Tag Archives: 2011 ASCO Annual Mtg.

2011 ASCO: Exelixis Reports Expanded Cabozantinib (XL184) Phase II Data For Advanced Ovarian Cancer; Six Deaths Reported

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Exelixis, Inc. reported expanded Phase 2 study data with respect to cabozantinib (XL184) use in advanced ovarian cancer patients at the recent 2011 American Society of Clinical Oncology Annual Meeting. The overall solid tumor Phase 2 safety and tolerability data reference six deaths, including two ovarian cancer patients.

Ronald J. Buckanovich, M.D., Ph.D., Assistant Professor, Departments of Internal Medicine & Obstetrics and Gynecology, University of Michigan

Exelixis, Inc. reported expanded Phase 2 study data with respect to cabozantinib (XL184) use in advanced ovarian cancer patients at the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting . The overall solid tumor Phase 2 safety and tolerability data refers to six deaths, including two ovarian cancer patients.

On May 19, 2011, we reported promising cabozantinib phase 2 solid tumor (including ovarian) data, which was presented at an ASCO press briefing held in advance of the 2011 ASCO Annual Meeting. As noted in our May 19 article, cabozantinib demonstrated excellent activity against several solid tumors, including ovarian cancer. In addition, we reported that cabozantinib showed promising activity in ovarian cancer patients independent of prior response to platinum drug-based therapies.

Ronald J. Buckanovich, M.D., Ph.D., Assistant Professor, Departments of Internal Medicine & Obstetrics and Gynecology, University of Michigan, presented the expanded cabozantinib Phase 2 data relating to use of the drug in advanced ovarian cancer patients, on June 4 at the 2011 ASCO Annual Meeting.

Ovarian Cancer Patient Population & Overall Response Rate

(Image Source: Exelixis, Inc.)

The cabozantinib trial is an ongoing phase 2 adaptive randomized discontinuation trial. As of the February 11, 2011 cut-off date, accrual in the cabozantinib study cohort was complete at 70 patients.

The 70 patients enrolled in the ovarian cancer cohort received oral cabozantinib (100 mg) daily over a 12 week “Lead-in Stage.” These patients had a minimum follow-up of at least 12 weeks and were thus evaluable for safety and the primary efficacy endpoint of response per RECIST (Response Evaluation Criteria in Solid Tumors).

Patient tumor response was assessed every 6 weeks. Receipt of cabozantinib treatment beyond the 12 week open label Lead-in Stage was based upon patient response: (1) patients with a partial response (PR) or complete response (CR) continued taking cabozantinib, (2) patients with stable disease (SD) were randomized to the cabozantinib treatment arm or the placebo treatment arm (collectively referred to as the “Blinded Randomized Stage”), and (iii) patients with progressive disease (PD) discontinued study treatment. The study primary endpoint was overall response rate (ORR) per RECIST in the Lead-in Stage, and progression free survival (PFS) in the Blinded Randomized Stage. Accrual in any cohort could be halted for high ORR or PD.

Approximately half of the 70 patients enrolled in the cohort were considered platinum drug-refractory/-resistant (49%), defined as a platinum drug-free interval of 6 months or less, and the remainder of patients (51%) had platinum-sensitive disease based on a platinum-free interval greater than 6 months.

The baseline patient tumor histologic characteristics are as follows: serous ovarian cancer (79%), clear cell ovarian cancer (4%), endometrioid ovarian cancer (6%), and other forms of ovarian cancer (11%)

More than half the patients (57%) received 2 or more prior lines of platinum therapy prior to trial enrollment. Some patients also had additional prior lines of therapy with agents such as pegylated liposomal doxorubicin (brand name: Doxil®) or topotecan (brand name: Hycamtin®) (32%), gemcitabine (brand name: Gemzar®) (29%), and VEGF (vascular endothelial growth factor) pathway inhibitors (10%).

Evidence of objective tumor regression was observed in 73% of patients with at least 1 post-baseline medical imaging scan. The best overall response rate per RECIST criteria was 24% (16 PRs and 1 CR). The overall Week-12 disease control rate (DRC = CR + PR + SD) was 53%. The Week-12 DCRs in the platinum drug-refractory, -resistant, and -sensitive groups were 36%, 39%, and 67%, respectively.

Based on an observed high rate of clinical activity, randomization was halted, and randomized patients were unblinded.  At this point, the unblinded randomized patients that were treated with placebo were allowed to “cross-over” to treatment with cabozantinib. Disease stabilization was experienced by some ovarian cancer patients who had progressive disease prior to treatment cross-over.

“These latest results in metastatic ovarian cancer demonstrate the potential broad utility of cabozantinib beyond bone-predominant types of cancers such as castration-resistant prostate cancer. The high rates of durable response with our dual inhibitor of MET and VEGFR2 compare favorably to those of other single-agent targeted therapies and cytotoxic agents in development,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “These results underscore the potential of cabozantinib in metastatic ovarian cancer, and we are in discussions with leading cooperative groups to plan further evaluation of cabozantinib in randomized trials for this indication.”

Activity in Platinum Drug-Sensitive, -Refractory, and -Resistant Disease

Ignace Vergote, M.D., Ph.D., senior author of the cabozantinib (XL184) ASCO presentation & Chairman, Leuven Cancer Institute, University of Leuven, European Union

(Image Source: Exelixis, Inc.)

Two of 11 patients (18%) with platinum refractory disease, defined as a platinum-free interval of <1 month, achieved a confirmed response (1 CR and 1 PR).

In the subset of patients with platinum-resistant disease, defined as a platinum-free interval of 1-6 months, 5 of 23 (22%) achieved a PR.

Ten of 36 patients (28%) with platinum sensitive disease achieved a PR.

A total of 37 patients experienced reductions in the ovarian cancer tumor marker CA-125 (cancer antigen-125), including 8 with decreases greater than 50%. There is no consistent concordance between CA-125 changes and tumor regression. The median duration of response has not yet been reached with 36 weeks of median follow-up.

“The continued activity of cabozantinib in a larger population of ovarian cancer patients is very encouraging, especially with respect to the clinical benefit observed in both platinum-sensitive and platinum-resistant/refractory disease. This activity profile has not been observed with other single-agent TKIs [tyrosine kinase inhibitors], and cabozantinib has the potential to be an important new treatment for ovarian cancer,” said Ignace Vergote, M.D., Ph.D., senior author of the presentation and Chairman of the Leuven Cancer Institute at the University of Leuven, European Union. “The high rate of disease control in platinum-resistant and platinum-refractory disease suggests that cabozantinib may help to address the substantial unmet medical need faced by patients who have sub-optimal responses to platinum-based therapies. I believe that further evaluation will help to define the potential role of cabozantinib in the treatment of ovarian cancer.”

General Safety & Tolerability Data 

Safety data are available for the 70 patients in the Lead-In phase of the cabozantinib study. The most common CTCAE (Common Terminology Criteria for Adverse Events) grade 3 or 4 adverse events (AEs), regardless of causality, were diarrhea (10%), fatigue (9%), palmar-plantar erythrodysesthesia  syndrome (also referred as “hand-foot syndrome”)(7%), vomiting (4%), abdominal pain (3%), hypomagnesemia (3%), and nausea, constipation, rash, increased transaminase, and hypertension (each 1%). At least one dose reduction was reported in 37% of patients. Less frequent important medical events, regardless of causality, were hemorrhage (11% all CTCAE grades, 0% CTCAE grade 3 or 4), venous thrombosis (6% all CTCAE grades, 4% CTCAE grade 3 or 4), and gastrointestinal perforation (6% all CTCAE grades, 0% CTCAE grade 3 or 4).

To access the cabozantinib clinical study data information, please visit www.exelixis.com/sites/default/files/pdf/ASCO_2011-XL184-Ovarian.pdf

Six Deaths Reported (Including Two Ovarian Cancer Patients)

If you examine the Exelixis press release dated June 4 (entitled, Exelixis’ Cabozantinib Demonstrates Encouraging Clinical Activity in Patients with Metastatic Ovarian Cancer — Disease control rate of 53% at week 12, response rate of 24%), which addresses data for cabozantinib use in advanced ovarian cancer patients, pay particular attention to the wording under the heading entitled, “Safety and Tolerability.”  Within the wording set forth under that heading, you will find the following statement: “Two cabozantinib-related grade 5 AEs [adverse events], one enterocutaneous fistula and one intestinal perforation, were reported after the Lead-In phase.” Pursuant to the CTCAE guidelines, a “grade 5 adverse event” is defined as “death related to AE [adverse event].”

We should also note that the two ovarian cancer deaths were summarized briefly in the ASCO presentation regarding cabozantinib use in advanced ovarian cancer.

The reporting of all six deaths is set forth in the Exelixis press release, dated June 5, 2011 (entitled, Exelixis’ Cabozantinib Demonstrates Broad Clinical Activity in Multiple Tumor Types), in similar fashion. Within this release, the sentence provided under the heading “Safety and Tolerability” states: “There were 6 (1%) cabozantinib-related grade 5 [adverse] events, all of which were reported after the Lead-In phase of the trial: respiratory compromise (breast cancer), hemorrhage (NSCLC [non-small cell lung cancer]), enterocutaneous perforation (ovarian cancer), intestinal perforation (ovarian cancer), gastrointestinal hemorrhage (pancreatic cancer), and death (CRPC [castrate resistant prostate cancer]).”

Exelixis Chief Executive Michael Morrissey said the safety statistics are consistent with targeted cancer therapies like cabozantinib that block a pathway used by tumor cells to secure blood vessels.

Cowen & Co analyst Eric Schmidt said the rate of cabozantinib treatment-related deaths — 1 percent — was “no different from what we have seen for every other Phase 1 and 2 trials here at ASCO.”

“While drug safety is of less concern in cancer indications than in others, the apparent morbidities associated with cabo[zantinib] use will confound interpretation of clinical benefit in a trial designed to show anything less than overall survival,” Canaccord analyst George Farmer said in a research note.

In a note to investors, Piper Jaffray analyst Edward Tenthoff said: “The company is exploring lower doses, but the concern is that cabo[zantinib] will not retain the impressive efficacy seen to date.”

Mr. Morrissey said Exelixis plans to move forward with the current daily 100 mg dose of the drug.

Dr. Nicholas J. Vogelzang (Director, Comprehensive Cancer Centers of Nevada) Discusses Mortalities in the Cabozantinib (XL184) Trial

Take Away Message

  • Cabozantinib demonstrates promising activity in both platinum drug-sensitive and platinum drug-resistant/-refractory ovarian cancer.
  • Week 12 overall disease control rate of 53%.
  • Response rates of 18% in platinum-refractory, 22% in platinum-resistant and 28% in platinum-sensitive patients.
  • Cabozantinib shows encouraging duration of response.
  • After 36 weeks of follow-up, median duration of response not reached.
  • Tolerability profile is consistent with that of other tyrosine kinase inhibitors (6 solid tumor patient deaths (1% of all solid tumor pts), including 2 ovarian cancer patients (3% of ovarian cancer pts)).
  • Discordant effects observed between CA-125 changes and clinical activity.
  • Simultaneous targeting of MET and VEGFR2 with cabozantinib results in robust effects in patients with advanced ovarian cancer.
  • Non-randomized expansion cohort is currently accruing in platinum-resistant/-refractory ovarian cancer.

About the MET & VEGFR2 Pathways

To learn more about (i) the role of MET in cancer, (ii) the relationship between the MET and VEGFR pathways, and (iii) the dual inhibition of MET and VEGFR2, visit http://www.metinhibition.com/.

About Cabozantinib (XL184)

Cabozantinib (XL184) is a potent, dual inhibitor of MET and VEGFR2. Cabozantinib is an investigational agent that provides coordinated inhibition of metastasis and angiogenesis to kill tumor cells while blocking their escape pathways. The therapeutic role of cabozantinib is currently being investigated across several tumor types. MET is upregulated in many tumor types, thus facilitating tumor cell escape by promoting the formation of more aggressive phenotypes, resulting in metastasis. MET-driven metastasis may be further stimulated by hypoxic conditions (i.e., deprivation of adequate oxygen supply) in the tumor environment, which are often exacerbated by selective VEGF-pathway inhibitors. In preclinical studies, cabozantinib has shown powerful tumoricidal, anti-metastatic and anti-angiogenic effects, including: (i) extensive apoptosis of malignant cells; (ii) decreased tumor invasiveness and metastasis; (iii) decreased tumor and endothelial cell proliferation; (iv) blockade of metastatic bone lesion progression; and (v) disruption of tumor vasculature.

About Exelixis

Exelixis, Inc. is a biotechnology company committed to developing small molecule therapeutics for the treatment of cancer. Exelixis is focusing its resources and development efforts exclusively on cabozantinib, its most advanced solely-owned product candidate, in order to maximize the therapeutic and commercial potential of this compound. Exelixis believes cabozantinib has the potential to be a high-quality, differentiated pharmaceutical product that can make a meaningful difference in the lives of patients. Exelixis has also established a portfolio of other novel compounds that it believes have the potential to address serious unmet medical needs. For more information, please visit the company’s web site at www.exelixis.com

Sources: 

Cabozantinib (XL184) Clinical Trial Information
Related Libby’s H*O*P*E*™ Postings
Related Libby’s H*O*P*E*™ Videos

2011 ASCO: Additional Phase III Study Data Support the Potential Role of Avastin in Newly-Diagnosed & Recurrent Ovarian Cancer

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Positive results from two bevacizumab (Avastin®) phase III clinical studies were presented at the 2011 American Society of Clinical Oncology Annual Meeting on June 4. The data reported add to the growing body of evidence in support of bevacizumab use to treat recurrent and newly-diagnosed ovarian cancer.

Positive results from two bevacizumab (Avastin®) phase III clinical studies were presented at the 2011 American Society of Clinical Oncology Annual Meeting on June 4. The data reported add to the growing body of evidence in support of bevacizumab use to treat recurrent and newly-diagnosed ovarian cancer.

About Bevacizumab (Avastin®)

A diagram illustrating the role of the VEGF protein in the formation of new blood vessels that support tumor growth. Click on the picture above to view a video regarding the mechanism of action with respect to bevacizumab (Avastin®). (Photo: Genentech)

“Angiogenesis” refers to the process of new blood vessel formation. When tissues need more oxygen, they release molecules that encourage blood vessel growth. Angiogenesis is a normal and vital process in human growth and development, as well as in wound healing. Unfortunately, cancer tumors also utilize this same process to enhance their own blood supply in order to nourish their aberrant growth.

Ovarian cancer is associated with high concentrations of vascular endothelial growth factor (VEGF), a protein associated with tumor growth and spread. Studies have shown a correlation between a high concentration of VEGF and ascites  (excess fluid in the body cavity) development, disease worsening, and a poorer prognosis in women with ovarian cancer.[1-2]

Bevacizumab is a humanized monoclonal antibody designed to specifically bind to the VEGF protein, which plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels through angiogenesis. The drug interferes with the tumor blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumor blood supply is thought to be critical to a tumor’s ability to grow and spread in the body (metastasize).

Bevacizumab is the first U.S. Food and Drug Administration (FDA) approved therapy designed to inhibit angiogenesis. Although FDA-approved for several forms of cancer, bevacizumab is not yet approved for the treatment of ovarian cancer. Patients treated with bevacizumab may experience side effects. In past clinical trials, some people treated with bevacizumab experienced serious and sometimes fatal side effects, related to gastrointestinal (GI) perforation, surgery and wound healing, and severe bleeding. For more information, review the Avastin BOXED WARNINGS and Additional Important Safety Information.

OCEANS Phase III Clinical Study: Women with Recurrent Platinum Sensitive Ovarian Cancer Experience 78% Response Rate & 52% Reduction In Disease Progression Risk

  • About the OCEANS Study

“OCEANS” is a multicenter, randomized, double-blind, placebo-controlled Phase III study in 484 women with platinum drug-sensitive recurrent ovarian, primary peritoneal or fallopian tube cancer.[3] Women in the OCEANS study received no more than one treatment regimen prior to study enrollment.  The OCEANS study randomized enrolled women to one of two clinical study arms:

Arm A: Intravenous carboplatin (area under the curve (AUC) 4; Day 1) + gemcitabine  (1,000 mg/m2; Day 1 & 8; brand name: Gemzar®) + placebo (Day 1) every 21 days x 6 cycles, followed by placebo maintenance every 21 days, until disease progression or unacceptable toxicity occurred.

Arm B: Carboplatin + gemcitabine + bevacizumab (15 mg/kg; Day 1) every 21 days x 6 cycles, followed by single agent bevacizumab maintenance every 21 days, until disease progression or unacceptable toxicity occurred.

The primary endpoint of the OCEANS study was progression free survival. The secondary endpoints of the study included overall survival, objective response, duration of response and safety profile.

  • OCEANS Study Data

Carol Aghajanian, M.D. speaks during the Oral Abstract Session: Gynecologic Cancer at the American Society of Clinical Oncology Annual Meeting on Saturday June 4, 2011. (Photo: ASCO/GMG/Silas Crews 2011)

Carol Aghajanian, M.D., chief of the gynecologic medical oncology service at Memorial Sloan-Kettering Cancer Center, presented the data from the OCEANS study comparing efficacy and safety of chemotherapy and antiangiogenic therapy in platinum drug-sensitive recurrent ovarian cancer.

Two hundred forty-two women were allocated to each study arm and the median follow-up period was 24 months. Patient characteristics were well-matched in the two treatment groups with regard to age (median age ~60), race (~91% white), performance status (~75%, PS = 0), histologic subtype (~80% serous), cytoreductive surgery (~11%), and platinum-free interval (defined as the time between finishing front-line platinum-based therapy and starting second-line chemotherapy) of more than 12 months (~60%). The study stratification variables were platinum-free interval (6 to 12 months vs. more than 12) and cytoreductive surgery for recurrent disease (yes vs. no).

The median number of chemotherapy cycles was six for each group, and a median of 11 cycles of bevacizumab or placebo was given. At least one-third of the patients received more than six cycles of carboplatin and gemcitabine, although slightly more of the placebo-treated group continued chemotherapy beyond six cycles.

Progression-free survival was significantly longer for women given bevacizumab (12.4 months vs. 8.4 months in the placebo-treated group (hazard ratio [HR]: 0.484; 95% confidence interval (CI) [0.388, 0.605]; p < 0.0001). These results were corroborated by the analyses of an independent review committee. Analyses according to platinum-free interval, cytoreductive surgery, age, and baseline performance status indicate a consistent benefit in all subgroups.

Objective response rate increased by 21.1% (p < 0.0001), from 57.4% in the placebo group to 78.5% in the bevacizumab treated group; duration of response increased from a median of 7.4 months to 10.4 months, respectively (HR: 0.534; 95% CI [0.408, 0.698]; p < 0.0001). Overall survival data are still premature, with median survival of 29.9 months in the placebo group and 35.5 months in the bevacizumab treatment group.

Sixty-five percent of the patients in the placebo group were withdrawn from the protocol due to disease progression, compared with only 41% of the treatment group, but 23% of the discontinuations in the bevacizumab group were due to adverse events, compared with only 5% in the placebo group. Much of this increase was due to grade 3 (or worse) adverse events; specifically hypertension and proteinuria associated with bevacizumab therapy. Overall, the safety profile of bevacizumab was consistent with past trials.

  • OCEANS Study Commentary

Dr. Aghajanian concluded that the OCEANS study results demonstrate a statistically significant and clinically relevant benefit when bevacizumab is added to carboplatin and gemcitabine. Aghajanian stated that this regimen should be considered a new option for the treatment of recurrent, platinum drug-sensitive ovarian cancer. As expected, the rate of adverse events was higher among patients who received bevacizumab, explained Dr. Aghajanian. “Hypertension and proteinuria were increased, but febrile neutropenia was the same in both arms.” “The safety data are reassuring and consistent with the known bevacizumab side-effect profile, and there were no new safety signals,” said Dr. Aghajanian.

“In advanced ovarian cancer, just as in advanced breast cancer, there is often an opportunity to intervene with different lines of chemotherapy,” said Andrew Seidman, M.D., attending physician for the breast cancer medicine service at Memorial Sloan-Kettering Cancer Center and professor of medicine at Weill Medical College of Cornell University. “There are many chapters in the story, so to speak,” said Dr. Seidman, who moderated a press briefing held in advance of the presentation. “We want to prolong each and every chapter in the disease, and make the story longer and ultimately improve survival. These trials results are certainly an important step in that direction.”

“Women with recurrent ovarian cancer need new treatment options, and it is therefore an important advance to halve the risk of disease progression in this incurable cancer,” said Hal Barron, M.D., chief medical officer and head of Roche Holdings Global Product Development. “These data add to the growing body of evidence supporting Avastin’s potential role in this disease, which includes two previously presented Phase III clinical trials [Gynecologic Oncology Group (GOG)-218 [4] & ICON7] in women with newly diagnosed ovarian cancer.”

In his discussion of the study, Anil K. Sood, M.D., professor and director of the Blanton-Davis Ovarian Cancer Research Program in the Departments of Gynecologic Oncology and Cancer Biology at the University of Texas M.D. Anderson Cancer Center, suggested that further understanding of the timing and dosing of bevacizumab should be pursued in light of (i) its great financial cost, and (ii) reports that inhibition of angiogenesis in animal models reduces primary cancer tumor growth, but accelerates invasion and metastasis — unintended consequences that might be linked to the failure of bevacizumab to extend overall survival in most clinical trials.

ICON7 Phase III Clinical Study:  Newly-Diagnosed Women with High-Risk Ovarian Cancer Experience 36% Reduction in Risk of Death

Gunnar Kristensen M.D., Ph.D. speaks during the Women's Cancers Press Briefing at the American Society of Clinical Oncology Annual Meeting on June 4, 2011. (Photo: ASCO/GMG/Scott Morgan 2011)

ICON7 was designed to investigate safety and efficacy of adding bevacizumab to standard chemotherapy in women with newly diagnosed ovarian cancer. [5] Gunnar Kristensen, M.D, Ph.D., senior consultant in the Department for Gynecologic Oncology of the Norwegian Radium Hospital located in Oslo, reported the Phase III clinical study results.

  • About the ICON7 Study

From December 2006 to February 2009, 1,528 women were randomized from 263 centers in 7 Gynecologic Cancer InterGroups. Eligible women with high-risk early FIGO (Federation of International Gynecology and Obstetrics) stage I or IIa (grade 3 or clear cell histology), capped ≤10%) or advanced (stage IIb-IV) epithelial ovarian, primary peritoneal or fallopian tube cancer were randomizsed (1:1) to one of two study arms:

Arm A: 6 cycles of 3 weekly chemotherapy (carboplatin AUC 5 or 6 and paclitaxel 175mg/m2) alone;  or

Arm B: Same chemotherapy as in Arm A, given concurrently with bevacizumab (7.5mg/kg) for 5 or 6 cycles, followed by continued 3-weekly single-agent bevacizumab maintenance therapy for 12 additional cycles (up to 12 months) or until disease progression (whichever event occurs first).

The baseline patient characteristics were balanced between both study arms: median age (57 years); ECOG Performance Status 0-1 (47%); high-risk early-stage disease (9%); poor prognosis patients (30%); histology (69% serous, 8% endometrioid, 8% clear cell).

  • Updated ICON7 Progression Free Survival Data

Data from the ICON7 study were presented for the first time at the 2010 European Society of Medical Oncology (ESMO) Congress. As reported at ESMO, chemotherapy-naïve ovarian cancer patients who received bevacizumab in combination with standard chemotherapy, and then continued with single agent bevacizumab maintenance therapy, experienced approximately 27% improvement (18.3 months versus 16 months) in the likelihood of living longer without the disease worsening (i.e., progression-free survival) compared to those women who received only chemotherapy (hazard ratio = 0.79, p=<0.0010), which corresponds to a 21% reduction in risk of cancer progression or death. The ICON7 data presented at ESMO was based upon mature progression-free survival results.

The updated ICON7 progression-free survival data presented at the ASCO annual meeting were consistent with the data reported last year at ESMO. In the updated analysis, women assigned to the bevacizumab arm experienced longer progression-free survival than those in the control group (19.8 months vs 17.4 months; HR, 0.87; p =.039). “There is a substantial prolongation of time to progression,” said Dr. Kristensen, adding that the gain was 2.4 months.

  • ICON7 Overall Survival Data Immature; But Clear Benefit To Women With “Poor Prognosis.” 

At a median follow-up of 28 months, there were fewer deaths among women who received bevacizumab than among those who received standard chemotherapy (178 vs 200). Although this represents a 15% overall reduction in mortality risk, the difference did not reach statistical significance (hazard ratio [HR], 0.85; P = .11). The final analyses for overall survival will be performed when 715 patient deaths have occurred. The current analysis was conducted because an interim analysis with at least 365 deaths was requested by the FDA and the European Medicines Agency for licensing consideration.

Although the overall survival data is not mature, a subgroup analysis of women with a “poor prognosis” (defined as FIGO stage III patients debulked to >1.0cm of visible diease or FIGO stage IV with debulking) was performed. Within this subgroup, there were 79 deaths within the bevacizumab arm and 109 deaths in the control arm. Based on this data, there was a 36% reduction in the risk of death (HR=0.64, 95% CI=0.48 to 0.85, p=0.0022 with p=0.015 for test for interaction (treatment/risk group)) among the poor prognosis subgroup.  This result was statistically significant. “We have previously shown that [the high-risk] group has a greater benefit from bevacizumab than the other patients,” said Dr. Kristensen. “For this group, there is a very clear gain for overall survival.”

  • ICON7 Study Commentary

“We conclude that the addition of concurrent and continued bevacizumab for 12 months does improve progression-free survival,” said Dr. Kristensen.  Kristensen also noted that, on the basis of an interim analysis involving approximately 53% of the number of deaths needed for the final analysis, there is an overall trend for improvement in overall survival.

“In this study, we see the ability of antiangiogenic therapy to delay the progression of ovarian cancer, this time in the first-line setting,” said Andrew Seidman, M.D. He added that previous studies have demonstrated the efficacy of bevacizumab in ovarian cancer. “These lend support to a potential role for bevacizumab as the first biologic agent to be used in this disease,” said Seidman, who moderated a press briefing during which study highlights were presented.

There are many strengths in a study like this, in that it addresses questions about the role of anti-VEGF therapies in this setting, said Anil Sood, M.D., who served as a discussant for this paper. “The randomized design is obviously a major strength.”

However, there are potential issues to examine, explained Dr. Sood. “One is the role of bevacizumab in the combination setting, compared with the maintenance setting.”

“How useful is bevacizumab in the combination setting up front? Is the real role for bevacizumab in the maintenance setting following initial chemotherapy,” he asked.

The issue of bevacizumab dosing was also raised by Dr. Sood. “One of the questions is whether higher doses are needed,” he said. “There are data emerging from other studies showing that lower doses are as efficacious, if not more so.”

References:

1/Rudlowski C, Pickart AK, Fuhljahn C, et. al. Prognostic significance of vascular endothelial growth factor expression in ovarian cancer patients: a long-term follow-up. Int J Gynecol Cancer. 2006 Jan-Feb;16 Suppl 1:183-9. PubMed PMID: 16515588.

2/Cooper BC, Ritchie JM, Broghammer CL, et. al. Preoperative serum vascular endothelial growth factor levels: significance in ovarian cancer. Clin Cancer Res. 2002 Oct;8(10):3193-7.  PMID: 12374688

3/Aghajanian C, Finkler NJ, Rutherford T, et. al. OCEANS: A randomized, double-blinded, placebo-controlled phase III trial of chemotherapy with or without bevacizumab (BEV) in patients with platinum-sensitive recurrent epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC). J Clin Oncol 29: 2011 (suppl; abstr LBA5007)[2011 American Society of Clinical Oncology Annual Meeting].

4/ Burger RA, Brady MF, Bookman MA, et. al. Phase III trial of bevacizumab in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): a Gynecologic Oncology Group study [GOG 218 Abstract]. J Clin Oncol 28:18s, 2010 (suppl; abstr LBA1).

5/Kristensen G, Perren T, Qian W., et. al. Result of interim analysis of overall survival in the GCIG ICON7 phase III randomized trial of bevacizumab in women with newly diagnosed ovarian cancer. J Clin Oncol 29: 2011 (suppl; abstr LBA5006) [2011 American Society of Clinical Oncology Annual Meeting].

Additional Sources & Helpful Information:

Bevacizumab (Avastin®) Clinical Trial Information

Related WORD of HOPE Ovarian Cancer Podcast™

Related Libby’s H*O*P*E*™ Postings

Related Libby’s H*O*P*E*™ Videos

  • To view videos regarding bevacizumab (Avastin®), click here.


2011 ASCO: EC145 Demonstrates 85 Percent Improvement in Progression-Free Survival for Treatment of Platinum Resistant Ovarian Cancer

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EC145, in combination with pegylated liposomal doxorubicin (Doxil®/Caelyx®) in patients with platinum-resistant ovarian cancer, met its primary endpoint by showing an 85 percent (2.3 month) improvement in median progression-free survival in the intent-to-treat population, and a 260 percent (4.0 month) improvement in a subset of folate receptor positive patients. The final EC145 phase 2 clinical study data were presented today at the 2011 American Society of Clinical Oncology Annual Meeting.

EC145 delivers a very potent vinca chemotherapy directly to cancer cells by targeting the folate receptor expressed on cancer cells, but not on most normal cells. Approximately 80-90 percent of ovarian and lung cancers express the receptor, as do many other types of cancer. Click on the picture above to view a video regarding EC145's mechanism of action. (Photo: Endocyte, Inc.)

Endocyte, Inc., a biopharmaceutical company developing targeted small molecule drug conjugates (SMDCs) and companion imaging diagnostics for personalized therapy, today announced that the phase 2 PRECEDENT trial, which is investigating the company’s lead drug candidate, EC145, in combination with pegylated liposomal doxorubicin (PLD)(brand name: Doxil®/Caelyx®) in patients with platinum-resistant ovarian cancer, met its primary endpoint by showing: (i) an 85 percent (2.3 month) improvement in median progression-free survival (PFS) in the intent-to-treat population, and (ii) a 260 percent (4.0 month) improvement in a subset of folate receptor positive patients. EC145 in combination with PLD showed limited additional toxicity compared to standard therapy with PLD alone. The most commonly occurring adverse events were neutropenia, small intestine obstruction, and palmar-plantar erythrodysesthesia (or hand-foot syndrome). EC145 is a therapeutic that targets the folate receptor and EC20 is a companion imaging diagnostic used to assess folate receptor presence.

These final PFS data from the PRECEDENT trial were presented today at the 2011 Annual Meeting of the American Society of Clinical Oncology (ASCO), in Chicago, Illinois and are available at http://investor.endocyte.com/events.cfm.

“I am encouraged by these data as EC145 is the first drug candidate to demonstrate a significant improvement in PFS in a randomized trial of patients with platinum-resistant ovarian cancer, a very challenging disease with a high unmet need. Historical data show that for these patients on standard therapy, PFS is approximately three months and overall survival is approximately twelve months. No new drug has been approved in the U.S. for this indication in over a decade,” said Wendel Naumann, M.D., Associate Director of Gynecologic Oncology at Blumenthal Cancer Center, Carolinas Medical Center. “In addition the companion imaging diagnostic, EC20, is designed to identify patients who over-express the targeted receptor and are most likely to respond to EC145. This represents a personalized therapeutic approach that I believe will help oncologists direct patients to the most promising treatment.”

EC145 Phase 2 PRECEDENT Clinical Study Data 

The Phase 2 PRECEDENT trial was an international, multi-center, randomized study of 149 women with platinum-resistant ovarian cancer. Patients were randomized to receive EC145 plus PLD or PLD alone at a standard dose until disease progression or death. The primary endpoint of the study was progression-free survival. Secondary endpoints included response rate and overall survival.

The EC145 phase 2 PRECEDENT trial results are summarized below.

  • 85 Percent (2.3 Month) Improvement in Median Progression-Free Survival for All Patients

Patients receiving EC145 in combination with PLD, regardless of folate receptor expression, had a median progression free survival of 5.0 months compared to 2.7 months for patients receiving single agent PLD. The hazard ratio for PFS was 0.626 (p=0.031). The overall response rate was 28 percent in the EC145 combination group versus 16 percent in the PLD-alone group. CA-125 (cancer antigen-125) responses were also more common in patients receiving EC145 in combination with PLD compared to those receiving PLD alone, with response rates (based on CA-125 blood serum measurement) of 38 percent and 19 percent, respectively.

  • 260 Percent (4.0 Month) Improvement in Median Progression-Free Survival for Patients Most Positive for Folate Receptor

The study also utilized EC20, an investigational companion imaging diagnostic that is designed to identify patients with folate receptor positive tumors. As expected, in the folate receptor positive patients the improvement in PFS was even greater. In the subpopulation most positive for the folate receptor, PFS increased 4.0 months from 1.5 months to 5.5 months. The hazard ratio for PFS was 0.381 (p=0.018). This represents more than a 60 percent reduction in the risk of progression and provides evidence supporting the mechanism of action through targeting of the folate receptor. The overall response rate was 22 percent in the EC145 combination group versus 7 percent in the PLD alone group. CA-125 responses were also more common in patients receiving EC145 in combination with PLD compared to those receiving PLD alone, 43 percent and 13 percent, respectively.

“We see tremendous potential for continued development of EC145 based on these data that demonstrate, for the first time, a significant improvement in PFS in patients with platinum resistant ovarian cancer,” said Ron Ellis, President and Chief Executive Officer of Endocyte. “We have already advanced EC145 into Phase 3 evaluation with the PROCEED trial, which has a similar design to the PRECEDENT trial, and plan to file for regulatory approval in the European Union based on the PFS data from the PRECEDENT study.”

Plan to File PRECEDENT Data for Conditional Approval in Europe

As a result of Endocyte’s interaction with the European Medicines Agency (EMA), including a meeting with the Scientific Advice Working Party and written advice from the Committee for Medicinal Products for Human Use (CHMP), the Company will prepare marketing applications for both EC145 and EC20. Based on feedback from the CHMP, Endocyte plans to seek conditional marketing authorization for patients with platinum-resistant ovarian cancer who test positive for the folate receptor using the EC20 companion imaging diagnostic.

Phase 3 PROCEED Trial Initiated

Endocyte recently announced the initiation of patient enrollment in the Phase 3 PROCEED trial of EC145, which is structured to replicate the PRECEDENT trial design. The Phase 3 trial is a randomized, double-blinded trial of EC145 in combination with PLD compared to PLD plus placebo. The patient population — those with platinum-resistant ovarian cancer — will be the same as in the PRECEDENT trial, and the primary endpoint will be progression-free survival in patients selected by EC20 as folate-receptor positive. The trial will also be statistically powered for overall survival as a secondary endpoint with projected enrollment in excess of 500 patients. The trial will be conducted in approximately 150 sites in the U.S., Canada, and Europe.  More information regarding the trial is available at www.clinicaltrials.gov.

About EC145

EC145 is a conjugate of the vitamin folate and a super-potent vinca alkaloid. Folate is required for cell division and rapidly dividing cancer cells often over-express folate receptors in order to capture enough folate to support cell division. By attaching a chemotherapy drug to folate through proprietary chemistry, EC145 targets cancer cells while avoiding most normal cells. This targeted approach is designed to provide treatment with super-potent drugs while lowering toxicity compared to standard chemotherapy.

About EC20

EC20 is a folate-targeted molecular imaging agent that is being developed as a non-invasive method to identify tumors that over-express folate receptors. These tumors are the molecular target of Endocyte’s folate-targeted therapeutic compounds such as EC145. To date, EC20 has been administered to over 500 patients and has been found to be well tolerated.

About Endocyte

Endocyte is a biopharmaceutical company developing targeted therapies for the treatment of cancer and inflammatory diseases. Endocyte uses its proprietary technology to create novel small molecule drug conjugates (SMDCs) and companion imaging diagnostics for personalized targeted therapies. The company’s SMDCs actively target receptors that are over-expressed on diseased cells, relative to healthy cells. This targeted approach is designed to enable the treatment of patients with highly active drugs at greater doses, delivered more frequently, and over longer periods of time than would be possible with the untargeted drug alone. The companion imaging diagnostics are designed to identify patients whose disease over-expresses the target of the therapy and who are therefore more likely to benefit from treatment.

Sources:

  • EC145 PRECEDENT Trial Results — 2011 American Society of Clinical Oncology Annual Meeting Poster Presentation, June 5, 2011. [Adobe Reader PDF document]
EC145 PROCEED Clinical Trial Information:
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Related Libby’s H*O*P*E*™ Postings:

2011 ASCO: Women with BRCA Gene Mutations Can Take Hormone-Replacement Therapy Safely After Ovary Removal

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Women with the BRCA1 or BRCA2 gene mutations, which are linked to a very high risk of breast and ovarian cancer, can safely take hormone-replacement therapy (HRT) to mitigate menopausal symptoms after surgical removal of their ovaries, according to new research from the Perelman School of Medicine at the University of Pennsylvania

Women with the BRCA1 or BRCA2 gene mutations, which are linked to a very high risk of breast and ovarian cancer, can safely take hormone-replacement therapy (HRT) to mitigate menopausal symptoms after surgical removal of their ovaries, according to new research from the Perelman School of Medicine at the University of Pennsylvania which will be presented on Monday, June 6 during the American Society for Clinical Oncology’s annual meeting. Results of the prospective study indicated that women with BRCA mutations who had their ovaries removed and took short-term HRT had a decrease in the risk of developing breast cancer.

Research has shown that in women who carry the BRCA gene mutations, the single most powerful risk-reduction strategy is to have their ovaries surgically removed by their mid-30s or early 40s. The decrease in cancer risk from ovary removal comes at the cost of early menopause and menopausal symptoms including hot flashes, mood swings, sleep disturbances and vaginal dryness — quality-of-life issues that may cause some women to delay or avoid the procedure.

Lead study author Susan M. Domchek, M.D., Associate Professor, Divison of Hematology-Oncology & Director, Cancer Risk Evaluation Program, Abramson Cancer Center, University of Pennsylvania

“Women with BRCA1/2 mutations should have their ovaries removed following child-bearing because this is the single best intervention to improve survival,” says lead author Susan M. Domchek, M.D., an associate professor in the division of Hematology-Oncology and director of the Cancer Risk Evaluation Program at Penn’s Abramson Cancer Center. “It is unfortunate to have women choose not to have this surgery because they are worried about menopausal symptoms and are told they can’t take HRT. Our data say that is not the case — these drugs do not increase their risk of breast cancer.”

Senior author Timothy R. Rebbeck, Ph.D., associate director of population science at the Abramson Cancer Center, notes that BRCA carriers may worry — based on other studies conducted in the general population showing a link between HRT and elevated cancer risk — that taking HRT may negate the effects of the surgery on their breast cancer risk. The message he hopes doctors will now give to women is clear: “If you need it, you can take short-term HRT. It doesn’t erase the effects of the oophorectomy.”

In the current study, Domchek, Rebbeck, and colleagues followed 795 women with BRCA1 mutations and 504 women with BRCA2 mutations who have not had cancer enrolled in the PROSE consortium database who underwent prophylactic oophorectomy, divided into groups of those who took HRT and those who did not. Women who underwent prophylactic oophorectomy had a lower risk of breast cancer than those who did not, with 14 percent of the women who took HRT after surgery developing breast cancer compared to 12 percent of the women who did not take HRT after surgery. The difference was not statistically significant.

Domchek says some of the confusion about the role of HRT in cancer risk elevation comes from the fact that the risks and benefits associated with HRT depend on the population of women studied. In this group of women — who have BRCA1/2 mutations and who have had their ovaries removed while they are quite young — HRT should be discussed and considered an option for treating menopausal symptoms. “People want to make hormone replacement therapy evil, so they can say ‘Don’t do it,'” she says. “But there isn’t one simple answer. The devil is in the details of the studies.”

By contrast, Penn researchers and their collaborators in the PROSE consortium have shown definitively that oophorectomy reduces ovarian and breast cancer incidence in these women, and reduces their mortality due to those cancers. But paying attention to the role that hormone depletion following preventive oophorectomy plays in women’s future health is also important.

“We know for sure that using HRT will mitigate menopausal symptoms, and we have pretty good evidence that it will help bone health,” she says. “Women need to be aware that going into very early menopause does increase their risk of bone problems and cardiovascular problems. And even if they aren’t going to take HRT, they need to be very attentive to monitoring for those issues. But they also need to know that HRT is an option for them and to discuss it with their doctors and other caregivers.”

About Penn Medicine

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.

About the University of Pennsylvania Perelman School of Medicine

Penn’s Perelman School of Medicine is currently ranked #2 in U.S. News & World Report’s survey of research-oriented medical schools and among the top 10 schools for primary care. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.

About the University of Pennsylvania Health System

The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania — recognized as one of the nation’s top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation’s first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

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2011 ASCO: EntreMed’s ENMD-2076 Demonstrates Clinical Activity in Recurrent, Platinum-Resistant Ovarian Cancer Patients

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EntreMed, Inc. announced that ENMD-2076 demonstrated clinical activity — a six-month progression free survival rate of 19% — when administered as a single agent to platinum drug-resistant recurrent ovarian cancer patients. The announcement is based upon interim phase 2 data presented today at the 2011 American Society of Clinical Oncology Annual Meeting. 

Ursula A. Matulonis, M.D., Medical Director, Gynecologic Oncology, Dana-Farber Cancer Institute; Associate Professor of Medicine, Harvard Medical School

EntreMed, Inc., a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer announced today the presentation of clinical data for its phase 2 study with ENMD-2076 in platinum drug-resistant recurrent ovarian cancer patients. The data were presented by the principal investigator for the study, Dr. Ursula A. Matulonis, medical director of gynecologic oncology at the Dana-Farber Cancer Institute and associate professor of medicine, Harvard Medical School, during a poster discussion session at the American Society of Clinical Oncology (ASCO) Annual Meeting being held June 3 – 7, 2011 in Chicago, Illinois.

The trial was an open-label, single-arm, multicenter study of ENMD-2076 dosed orally as a single agent in patients with platinum-resistant recurrent ovarian, peritoneal or fallopian tubal cancer. The study was conducted at six sites in the United States and Canada and included the Dana-Farber Cancer Institute, Indiana University Melvin & Bren Simon Cancer Center, University of Chicago Medical Center, Memorial Sloan-Kettering Cancer Center, University of Colorado Cancer Center, and Princess Margaret Hospital. Sixty-four patients were enrolled, of which 57 were evaluable at the time of the presentation. The primary endpoint for the study was progression-free survival rate at six months. Secondary end-points include response rate, duration of response, and overall survival.

ENMD-2076 demonstrated clinical activity when administered daily orally as a single agent. Interim data from 57 evaluable patients showed a six-month progression free survival rate of 19 percent. Of the evaluable patients, four patients achieved a partial response and 30 patients achieved stable disease as measured by RECIST v1.1. Median overall survival has not yet been reached. The side effect profile was consistent with activity against ENMD-2076’s molecular targets, in particular, VEGFR2 (vascular endothelial growth factor receptor-2) and Aurora A. Studies to evaluate potential markers of ENMD-2076 in this patient group are ongoing.

Dr. Matulonis commented on the results of the study, “ENMD-2076 has demonstrated impressive anti-cancer activity in platinum-resistant ovarian cancer which is notoriously difficult to treat, and these patients have few options.”

EntreMed’s chief medical officer, Carolyn F. Sidor, M.D., M.B.A., added, “These results are very encouraging as they support further development of ENMD-2076 and also help us clarify its developmental path in ovarian cancer. We are currently designing the next clinical trial in this indication and look forward to opportunities to make ENMD-2076 available to ovarian cancer patients in the future.”

About ENMD-2076

ENMD-2076 is an orally-active, Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. ENMD-2076 has been shown to inhibit a distinct profile of angiogenic tyrosine kinase targets in addition to the Aurora A kinase. Aurora kinases are key regulators of mitosis (cell division), and are often over-expressed in human cancers. ENMD-2076 also targets the VEGFR, Flt-3 and FGFR3 kinases which have been shown to play important roles in the pathology of several cancers. ENMD-2076 has shown promising activity in phase I clinical trials in solid tumor cancers, leukemia, and multiple myeloma. While ENMD-2076 is currently in a phase 2 trial in ovarian cancer, preclinical and clinical activities are ongoing in assessing the compound’s applicability in other forms of cancer.

To view an Adobe Reader PDF copy of the presentation, visit http://www.entremed.com/files/umatulonis_enmd_2076_p2_ovarian.pdf

About EntreMed

EntreMed, Inc. is a clinical-stage pharmaceutical company committed to developing ENMD-2076, a selective angiogenic kinase inhibitor, for the treatment of cancer. ENMD-2076 is currently in a multi-center phase 2 study in ovarian cancer and in several phase 1 studies in solid tumors, multiple myeloma, and leukemia.

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2011 ASCO: Matching Targeted Therapies To Specific Tumor Gene Mutations Key to Personalized Cancer Treatment

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Customizing targeted therapies to each tumor’s molecular characteristics, instead of a “one-size-fits-all” approach by tumor type, may be more effective for some types of cancer, according to research presented today at the American Society of Clinical Oncology annual meeting by the M.D. Anderson Cancer Center. In patients with end-stage disease, matched patients achieved a 27% response rate, versus 5% in those unmatched.

Customizing targeted therapies to each tumor’s molecular characteristics, instead of a “one-size-fits-all approach” by tumor type, may be more effective for some types of cancer, according to research conducted by The University of Texas M.D. Anderson Cancer Center.

Apostolia M. Tsimberidou, M.D., Ph.D., Associate Professor, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas

M.D. Anderson’s phase I clinical study findings were presented today on the opening press program of the 47th Annual Meeting of the American Society of Clinical Oncology. Apostolia-Maria Tsimberidou, M.D., Ph.D., associate professor in the M.D. Anderson Department of Investigational Cancer Therapeutics, and the principal investigator of the study, presented the data.

Marking the largest scale on which this approach has been examined to date, the study analyzed the results of matching targeted therapies with specific gene mutations in patients. The data indicated that this strategy was associated with higher rates of response, survival and failure-free survival than observed in non-matched patients.

Pairing Patient and Treatment

“This preliminary study strongly suggests that molecular analysis is needed to use the right drug for the right patient. Up to this point, we have treated tumor types, but this study shows we cannot treat all patients with a tumor type the same way. We need to take into consideration a number of factors, and this study suggests that a personalized approach is needed to improve clinical outcomes for patients with cancer,” said Tsimberidou.

The identification of pathways involved in carcinogenesis, metastasis and drug resistance; new technologies enabling tumor molecular analysis; and the discovery of targeted therapies have stimulated research focusing on the use of targeted agents as part of a personalized medicine approach, she said.

“Over the past decades, a personalized medicine approach using Gleevec has changed the way we treat chronic myeloid leukemia, as well as survival rates,” said Razelle Kurzrock, M.D., professor and chair of the M.D. Anderson Department of Investigational Cancer Therapeutics. “We wanted to apply a similar approach to solid tumors.”

“Ultimately, to best match treatments to patients and offer the most therapeutic benefit, assessing a patient’s molecular markers has to become the standard at diagnosis. … 

This study affirms what we in the cancer community have been talking about for a decade – matching drugs to patients. The time is now. The drugs are here. The technology is here, and with our program at M.D. Anderson we can bring the two together in hopes to offer the most personalized care for our patients. …”

–Razelle Kurzrock, M.D., Professor & Chair, Department of Investigational Cancer Therapeutics, University of Texas M.D. Anderson Cancer Center

Research Methods and Results

In the initial analysis, Tsimberidou analyzed 1,144 patients with metastatic or inoperable cancer who underwent testing for molecular aberrations at M.D. Anderson. Their median age was 58, and the median number of prior treatments was four. Of these patients, 460 had one or more gene aberrations, including:

  • 10 percent with a PIK3CA mutation;
  • 18 percent with a KRAS mutation;
  • 8 percent with a NRAS mutation;
  • 17 percent with a BRAF mutation;
  • 3 percent with an EGFR mutation;
  • 2 percent with a CKIT mutation;
  • 21 percent with a PTEN loss; and
  • 37 percent with a p53 mutation

Patients with gene aberrations were treated on clinical trials with matched targeted agents, when available. Regimens included one or more therapies targeting PIK3CA, mTOR, BRAF, MEK, multikinases, KIT or EGFR. Outcomes of patients with gene aberrations treated with matched therapy were compared with those patients with gene aberrations who were not treated with matched therapy because of issues such as eligibility, study availability; insurance coverage and/or logistical problems with the study calendar.

For the 175 patients with one aberration, the response rate was 27 percent with matched targeted therapy. The response rate was 5 percent in 116 patients when treated with non-matched therapy.

Patients who received matched targeted therapy had median survival of 13.4 months, while median survival for patients treated with unmatched targeted therapy was nine months. Median failure-free survival in patients who received matched targeted therapy was 5.2 months, compared to 2.2 months for patients who received unmatched targeted therapy.

Further Research Needed

These preliminary results merit further investigation and confirmatory, prospective studies are needed, especially because the study was not a randomized study and therefore biases could influence the results.

“M.D. Anderson’s goal is to better understand the biology involved in each patient’s carcinogenesis by testing each tumor for genetic abnormalities driving tumor growth to guide treatment selection. This strategy will lead to the optimization of personalized therapy,” Tsimberidou said.

Another goal is to match targeted therapies to patients earlier in treatment.

“When Gleevec was first introduced, it was tested in patients in blast crisis and the response rate was about 15 percent. In contrast, when tested in the front line setting, and with the introduction of similar but increasingly potent second- and third-generation drugs, patients’ response rate was close to 100 percent, and now their expected survival is 25 years and counting,” said Kurzrock. “Ultimately, to best match treatments to patients and offer the most therapeutic benefit, assessing a patient’s molecular markers has to become the standard at diagnosis.”

About the Phase I Program – The Time is Now

The M.D. Anderson’s Phase I program is the largest of its kind and accounts for the majority – but not all – of the institution’s earliest clinical studies. In 2010, of the 11,000 patients who participated in M.D. Anderson clinical trials, more than 1,150 were enrolled in one of the 120 Phase I trials in the program.

Currently, tumors are tested for up to 12 molecular aberrations, but at the rate technology is rapidly advancing, Kurzrock expects that number to climb to more than 100 in the near future.

Patients treated in the Phase I Program are typically very ill and all other approved therapies have failed them. Yet they are “fighters” who are willing to try anything, including studies not specific to their diagnosis to test the effectiveness of a new drug, drug combination or delivery method, said Kurzrock.

“This study affirms what we in the cancer community have been talking about for a decade – matching drugs to patients,” said Kurzrock. “The time is now. The drugs are here. The technology is here, and with our program at M.D. Anderson we can bring the two together in hopes to offer the most personalized care for our patients.”

In addition to Tsimberidou and Kurzrock, other authors on the all-M.D. Anderson study included N. G. Iskander, David S. Hong, M.D., Jennifer J. Wheler, M.D., Siqing Fu, M.D., Ph.D., Sarina A. Piha-Paul, M.D., Aung Naing, M.D., Gerald Falchook, Filip Janku, M.D., Ph.D., all assistant professors of the Department of Investigational Cancer Therapeutics; Raja Luthra, Ph.D., professor, Department of Hematopathology, Research and Sijin Wen, Ph.D., Division of Quantitative Sciences.

Libby’s H*O*P*E*™ Commentary — Use of Molecular Profiling and Chemosensitivity Testing To Determine Individualized Ovarian Cancer Treatment

It is wonderful that various medical research institutions, including M.D. Anderson, are beginning to match targeted therapies to a patient’s specific molecular tumor characteristics. This approach is generally referred to as “molecular profiling,” and it represents one promising method of matching an individual cancer patient to an effective therapy. As noted in the related Libby’s H*O*P*E*™ postings set forth below, there are several medical and scientific institutions which are pursuing development of molecular profiling for clinical study use. In the most recent related posting listed below, we discuss the molecular profile testing that is commercially available through The Clearity Foundation and Caris Life Sciences.

In the future, it may be helpful to use a form of chemosensitivity testing (e.g., the type of testing provided by Precision Therapeutics, Rational Therapeutics, and the Weisenthal Cancer Group), which is based upon the measurement of actual cancer cell death, as a second method to match a cancer patient to a potential drug or drug combination within the context of a clinical study. In fact, we would like to see a future prospective, randomized ovarian cancer clinical trial in which enrolled women are provided with treatment after assignment to one of three clinical trial arms:  (i) treatment based upon the standard of care (e.g., paclitaxel and carboplatin), (ii) treatment based upon molecular profiling, or (iii) treatment based upon chemosensitivity testing.  This type of study may uncover additional ovarian cancer treatment insights (both molecular and functional) with respect to the most lethal gynecologic cancer, while ultimately helping women with forms of the disease that may not possess a known molecular characteristic that is potentially “targetable” by an existing clinical trial drug or compound.

This combination of “bottom-up” scientific research (i.e., molecular profiling) performed side-by-side with “top-down” research (i.e., chemosensitivity testing) may represent an effective and efficient approach — albeit provocative — for evaluation of optimal personalized ovarian cancer treatment.

It is important to note that Libby’s H*O*P*E*™ and its founder Paul Cacciatore do not receive financial renumeration or benefit of any kind from the companies referred to in the paragraphs above.

About the University of Texas M.D. Anderson Cancer Center

The University of Texas M.D. Anderson Cancer Center in Houston ranks as one of the world’s most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For seven of the past nine years, including 2010, M.D. Anderson has ranked No. 1 in cancer care in “America’s Best Hospitals,” a survey published annually in U.S. News & World Report.

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ASCO 2011: Genetic Biomarker Predicts Taxane Drug-Induced Neuropathy

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A new study has identified the first genetic biomarkers for taxane-induced peripheral neuropathy, a potentially severe complication of taxane chemotherapy that affects nerves in about one-third of patients with cancer receiving such treatment.

ASCO Releases Studies From Upcoming Annual Meeting – Important Advances in Targeted Therapies, Screening, and Personalized Medicine

The American Society of Clinical Oncology (ASCO) today highlighted several studies in a press briefing from among more than 4,000 abstracts publicly posted online at http://www.asco.org in advance of ASCO’s 47th Annual Meeting. An additional 17 plenary, late-breaking and other major studies will be released in on-site press conferences at the Annual Meeting.

The meeting, which is expected to draw approximately 30,000 cancer specialists, will be held June 3-7, 2011, at McCormick Place in Chicago, Illinois. The theme of this year’s meeting is “Patients. Pathways. Progress.”

“This year marks the 40th anniversary of the signing of the National Cancer Act, a law that led to major new investments in cancer research. Every day in our offices, and every year at the ASCO meeting, we see the results of those investments. People with cancer are living longer, with a better quality of life, than ever before,” said George W. Sledge Jr., M.D., President of ASCO, Ballve-Lantero Professor of Oncology and professor of pathology and laboratory medicine at the Indiana University School of Medicine.

“With our growing understanding of the nature of cancer development and behavior, cancer is becoming a chronic disease that a growing number of patients can live with for many years,” said Dr. Sledge. “The studies released today are the latest examples of progress against the disease, from new personalized treatments, to new approaches to screening and prevention.”

New study results involving a genetic marker which can predict taxane drug-induced neuropathy were highlighted today in the ASCO press briefing, as summarized below.

Genetic Biomarker Predicts Taxane-Induced Neuropathy

A new study has identified the first genetic biomarkers for taxane drug-induced peripheral neuropathy, a potentially severe complication of taxane chemotherapy that affects nerves in about one-third of patients with cancer receiving such treatment. The finding may eventually lead to a simple blood test to determine whether a patient is at high risk for neuropathy.

Bryan P. Schneider, M.D., Physician & Researcher, Indiana University Melvin & Bren Simon Cancer Center; Associate Director, Indiana Institute for Personalized Medicine

“If these findings can be replicated, this may allow physicians to know prior to recommending therapy whether the patient is at an inordinate risk for developing taxane-induced neuropathy,” said Bryan P. Schneider, M.D., lead author and a physician/researcher at the Indiana University Melvin and Bren Simon Cancer Center and Associate Director for the Indiana Institute for Personalized Medicine. “This may allow for better counseling, use of alternative drugs or schedules, or omission of taxanes in the appropriate settings. These genetic findings might also provide insight into the mechanism of this side effect and help develop drugs to prevent this toxicity altogether.”

Such damage to the nerves can cause pain and numbness and limit the dose of chemotherapy a patient can receive. While only a few factors seem to predict which patients are likely to get peripheral neuropathy, including a history of diabetes and advanced age, genetic variations may explain why some patients are more sensitive to taxane drugs.

The authors conducted a genome wide association study on 2,204 patients enrolled in an Eastern Cooperative Oncology Group breast cancer clinical trial (E5103) in which all patients received taxane-based chemotherapy, namely paclitaxel (Taxol). The study looked for variations in DNA (deoxyribonucleic acid) called single nucleotide polymorphisms, or SNPs (pronounced “snips”), by evaluating more than 1.2 million SNPs in each patient.  A SNP is a DNA sequence variation which occurs when a single nucleotide — A (adenine), T (thymine), C (cytosine), or G (guanine) — in the genome (or other shared sequence) differs between two individuals, or between paired chromosomes located within the nucleus of an individual’s cells.

With a median follow-up of 15 months, the study identified genetic subgroups that were markedly more likely to develop peripheral neuropathy.

Those who carried two normal nucleotides in the RWDD3 gene had a 27 percent chance of experiencing neuropathy; those who carried one normal nucleotide and one SNP had a 40 percent risk; and those who carried two SNPs had a 60 percent risk.

In contrast, those who carried two normal nucleotides in the TECTA gene had a 29 percent chance of experiencing neuropathy; those who carried one normal nucleotide and one SNP had a 32 percent risk; and those who carried two SNPs had a 57 percent risk.

The study also found that older patients and African Americans were much more likely to have peripheral neuropathy, and further analysis of SNPs in these groups is underway.

The authors plan to continue their work in additional trials to validate these findings and to determine whether a different type or schedule of taxane therapy would result in less neuropathy in the more susceptible genetic groups. The authors also are collaborating with neurobiologists to understand why these genetic variations might make the nerves more sensitive to these drugs.

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ASCO 2011: Novel Multi-targeted Agent Cabozantinib (XL184) Has Significant Effect on Several Advanced Solid Tumors

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Cabozantinib (XL184) demonstrated high rates of disease control in patients with prostate, ovarian and liver cancers. The investigators concluded that cabozantinib exhibits clinical activity in ovarian cancer patients with advanced disease, regardless of prior platinum drug status, as reflected by the high rates of response. 

ASCO Releases Studies From Upcoming Annual Meeting – Important Advances in Targeted Therapies, Screening, and Personalized Medicine

The American Society of Clinical Oncology (ASCO) today highlighted several studies in a press briefing from among more than 4,000 abstracts publicly posted online at http://www.asco.org in advance of ASCO’s 47th Annual Meeting. An additional 17 plenary, late-breaking and other major studies will be released in on-site press conferences at the Annual Meeting.

The meeting, which is expected to draw approximately 30,000 cancer specialists, will be held June 3-7, 2011, at McCormick Place in Chicago, Illinois. The theme of this year’s meeting is “Patients. Pathways. Progress.”

“This year marks the 40th anniversary of the signing of the National Cancer Act, a law that led to major new investments in cancer research. Every day in our offices, and every year at the ASCO meeting, we see the results of those investments. People with cancer are living longer, with a better quality of life, than ever before,” said George W. Sledge Jr., M.D., President of ASCO, Ballve-Lantero Professor of Oncology and professor of pathology and laboratory medicine at the Indiana University School of Medicine.

“With our growing understanding of the nature of cancer development and behavior, cancer is becoming a chronic disease that a growing number of patients can live with for many years,” said Dr. Sledge. “The studies released today are the latest examples of progress against the disease, from new personalized treatments, to new approaches to screening and prevention.”

The study results from a phase II clinical trial involving cabozantinib (XL184) were highlighted today in the ASCO press briefing, as summarized below.

Novel Multi-targeted Agent Cabozantinib (XL184) Has Significant Effect on Several Advanced Solid Tumors, and Can Shrink or Eliminate Bone Metastases 

Cabozantinib (XL184) – an oral inhibitor of MET and VEGFR2 kinases involved in the development and progression of many cancers – showed strong responses in patients with various advanced cancers in a phase II trial. The drug demonstrated particularly high rates of disease control for advanced prostate, ovarian and liver cancers, which are historically resistant to available therapies. The drug also fully or partially eliminated bone metastases in patients with breast and prostate cancers and melanoma.

Michael S. Gordon, M.D., President & Chief Executive Officer, Pinnacle Oncology Hematology.

“Cabozantinib appears to have significant effects on several treatment-resistant tumors, as well as impressive effects on bone metastases. In addition, these effects are associated with rapid improvement in pain, a reduction in opiate narcotic requirements and improvement in anemia,” said lead author Michael S. Gordon, M.D., a medical oncologist at Pinnacle Oncology Hematology located in Scottsdale, Arizona. “The implications of these results are very exciting—it is unusual to find a targeted therapy, absent of a molecular mutation in tumors, that works in bony disease and has this activity.”

To be eligible for the study, patients had to have advanced, progressive solid tumors, with or without bone metastases. Of 398 evaluable patients (of 483 enrolled in the trial), 39 percent had bone metastases at baseline. Patients received cabozantinib over 12 weeks. The trial was designed as a “discontinuation” trial, in which those who had partial responses stayed on the drug; those with stable disease were randomized to cabozantinib or placebo; and patients with progressive disease were removed from the trial. This novel type of clinical trial design more quickly evaluates the disease-stabilizing activity of growth-inhibitory agents like cabozantinib, compared to the traditional model of randomizing all patients to either the experimental arm or placebo.

Among 398 patients evaluable with all types of cancer included in the trial, the collective overall response rate was 9 percent (34 of 398). The highest disease control rates (partial response and stable disease) at week 12 were 76 percent for liver cancer (22 of 29 patients), 71 percent for prostate cancer (71 of 100 patients), and 58 percent for ovarian cancer (32 of 51 patients). [emphasis added].

Of the 51 evaluable ovarian cancer patients noted above, 28 are platinum drug resistant, 17 are platinum drug sensitive, and 6 have unknown status. The median number of systemic treatments prior to trial enrollment was 2. The overall response rate (complete response and partial response based on modified RECIST criteria) for ovarian cancer was 12/51 (24%).  Upon breakdown, the response rate was 5/28 (18%) for platinum drug resistant patients, and 5/17 (29%) for platinum drug sensitive patients. Five additional partial responses await confirmation. After a median follow-up of 4 months (range: 1 to 11 months), the median duration of response and median progression free survival have not been reached. The most common related adverse events ( ≥grade 3) among ovarian cancer patients were hand-foot syndrome (10%), diarrhea (8%) and fatigue (4%). Drug dose reductions and permanent discontinuations for adverse events occurred in 43% and 10% of the ovarian cancer patients, respectively. Based on these findings, the investigators concluded that cabozantinib exhibits clinical activity in ovarian cancer patients with advanced disease, regardless of prior platinum drug status, as reflected by the high rates of response. [emphasis added] Accordingly, randomization in the ovarian cancer cohort was halted & patients unblinded due to the observed high efficacy.

Fifty-nine of 68 patients with bone metastases (including patients with breast and prostate cancers and melanoma) experienced either partial or complete disappearance of the cancer on bone scans, often with significant pain relief and other improved cancer-related symptoms.

The reduction of bone metastases and pain relief was an unexpected finding in this study, Dr. Gordon said. Independent review by radiologists confirmed that bone metastases disappeared in the majority of patients who had bone metastases when they entered the study. The majority of these patients had castration-resistant prostate cancer (CRPC), but patients with breast cancer and melanoma also had disappearance of bone metastases. Bone metastases greatly contribute to morbidity and mortality in patients with these types of cancer, which typically spread to the bone.

Due to these results, the study has been expanded to include more CRPC patients. Similarly, the high rate of lasting responses in ovarian cancer patients led researchers to also expand the study to evaluate the drug’s effect on patients with a particularly resistant form of the disease known as platinum drug resistant/refractory ovarian cancer. [emphasis added]

This study expansion results will help determine the design of future phase III trials, which will assess whether the drug extends patients lives or has other longer-term benefits among patients with specific cancer types. At present, cabozantinib is being investigated for use as a single agent. Additional studies will evaluate the efficacy and tolerability of appropriate combinations with other agents for future indications.

For the solid tumor patients collectively, the most common grade three or above adverse events were fatigue (9 percent) and hand-foot syndrome (8 percent). Dose reductions were required in 41 percent of patients due to side effects; 12 percent were removed from the trial for adverse events.

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Cabozantinib (XL184) Clinical Trials:

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ASCO 2011: Maintenance Therapy With PARP Inhibitors Could Play Important Role in Treatment of Recurrent Ovarian Cancer

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A randomized phase II clinical trial showed that the oral PARP inhibitor drug olaparib (AZD2281), given after chemotherapy, improved progression-free survival in women with the most common type of recurrent ovarian cancer.

ASCO Releases Studies From Upcoming Annual Meeting – Important Advances in Targeted Therapies, Screening, and Personalized Medicine

The American Society of Clinical Oncology (ASCO) today highlighted several studies in a press briefing from among more than 4,000 abstracts publicly posted online at http://www.asco.org in advance of ASCO’s 47th Annual Meeting. An additional 17 plenary, late-breaking and other major studies will be released in on-site press conferences at the Annual Meeting.

The meeting, which is expected to draw approximately 30,000 cancer specialists, will be held June 3-7, 2011, at McCormick Place in Chicago, Illinois. The theme of this year’s meeting is “Patients. Pathways. Progress.”

“This year marks the 40th anniversary of the signing of the National Cancer Act, a law that led to major new investments in cancer research. Every day in our offices, and every year at the ASCO meeting, we see the results of those investments. People with cancer are living longer, with a better quality of life, than ever before,” said George W. Sledge Jr., M.D., President of ASCO, Ballve-Lantero Professor of Oncology and professor of pathology and laboratory medicine at the Indiana University School of Medicine.

“With our growing understanding of the nature of cancer development and behavior, cancer is becoming a chronic disease that a growing number of patients can live with for many years,” said Dr. Sledge. “The studies released today are the latest examples of progress against the disease, from new personalized treatments, to new approaches to screening and prevention.”

The study results from a phase II clinical trial involving maintenance therapy with the PARP (poly (ADP-ribose) polymerase) inhibitor olaparib were highlighted today in the ASCO press briefing, as summarized below.

Randomized Study Shows that Maintenance Therapy With PARP Inhibitors Could Play Important Role in Treatment of Recurrent Ovarian Cancer

A phase II randomized trial showed that maintenance treatment with the oral PARP inhibitor drug olaparib (AZD2281) improved progression-free survival by about four months in women with the most common type of relapsed ovarian cancer. This is the first randomized trial to demonstrate a benefit for maintenance therapy for recurrent ovarian cancer, and the first randomized trial in ovarian cancer of a PARP inhibitor– a novel class of molecularly targeted drugs.

The results of this study, if confirmed in larger trials, could lead to a new treatment approach for recurrent ovarian cancer in which drugs like olaparib are given over a long period of time to prevent recurrences or prolong remissions. This somewhat novel approach, called maintenance therapy, has already proven useful in lung cancer. Standard treatment for ovarian cancer includes platinum-based chemotherapy. After this regimen, patients are observed until recurrence, and then treated with another course of chemotherapy. While some tumors respond well to chemotherapy, the regimens are too toxic for patients to take continuously, and clinical trials have not shown any benefit for extended courses of chemotherapy.

Jonathan A. Ledermann, M.D., Lead Author & Principal Investigator of PARP Maintenance Study; Professor, Medical Oncology, UCL Cancer Institute, University College London

“A well-tolerated antitumor agent that could be used for months or perhaps years as maintenance therapy after standard chemotherapy could be a big step forward and ultimately extend survival,” said lead author Jonathan A. Ledermann, M.D., principal investigator of the study and Professor of Medical Oncology at UCL Cancer Institute, University College London. “This study demonstrates proof of principle for the concept of maintenance therapy in ovarian cancer using a PARP inhibitor. Our progression-free survival difference was very impressive and better than we anticipated.”

The multicenter, international study randomized 265 women with high-grade serous ovarian cancer to either olaparib or placebo. Patients were enrolled in the trial within 8 weeks of having achieved either a complete or partial response to platinum-based treatment. PARP inhibitors have been shown to work better in patients whose tumors have responded to platinum.

In the study, the progression-free survival (PFS) – the amount of time during and after treatment in which the cancer does not return – was significantly longer in the group receiving olaparib than the placebo group, with a median of 8.4 months versus 4.8 months. At the time of data analysis, half the patients randomized to olaparib (68 patients) had not relapsed and were still receiving the drug, while only 16 percent (21 patients) remained on placebo – so overall survival data were not yet available for analysis.

Adverse events were more commonly reported in the group receiving olaparib than placebo, including nausea, fatigue, vomiting, and anemia, but the majority of these were not severe. Dose reductions to manage side effects were allowed in the study and were more prevalent in the olaparib group (23 percent) compared to the placebo group (7 percent).

Olaparib inhibits the enzyme poly (ADP-ribose) polymerase — abbreviated “PARP” — which is involved in DNA (deoxyribonucleic acid) repair. Up to half of women with high-grade serous ovarian cancer – the most common type of ovarian cancer – may have a DNA repair deficiency that makes them more susceptible to treatment with PARP inhibitors.

A number of PARP inhibitors are being studied in phase II and phase III clinical trials, as single agents and in combination with standard chemotherapies and radiation, in some types of breast and ovarian cancers believed to have DNA repair defects.

Sources:

PARP Clinical Trials:
Resources:
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Related Libby’s H*O*P*E*™ Videos Re PARP Inhibitors


2011 ASCO: Screening With CA-125 & Transvaginal Ultrasound Does Not Reduce Ovarian Cancer Death Rate, Results in High Number of False Positives

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Findings from a large, long-term study – the Prostate, Lung, Colorectal and Ovarian (PLCO) Screening Trial – showed that using a CA-125 blood test and transvaginal ultrasound for early detection of ovarian cancer did not reduce the risk of dying from the disease, and resulted in a large number of false positives and related follow-up procedures.

ASCO Releases Studies From Upcoming Annual Meeting – Important Advances in Targeted Therapies, Screening, and Personalized Medicine

The American Society of Clinical Oncology (ASCO) today highlighted several studies in a press briefing from among more than 4,000 abstracts publicly posted online at http://www.asco.org in advance of ASCO’s 47th Annual Meeting. An additional 17 plenary, late-breaking and other major studies will be released in on-site press conferences at the Annual Meeting.

The meeting, which is expected to draw approximately 30,000 cancer specialists, will be held June 3-7, 2011, at McCormick Place in Chicago, Ill. The theme of this year’s meeting is “Patients. Pathways. Progress.”

“This year marks the 40th anniversary of the signing of the National Cancer Act, a law that led to major new investments in cancer research. Every day in our offices, and every year at the ASCO meeting, we see the results of those investments. People with cancer are living longer, with a better quality of life, than ever before,” said George W. Sledge Jr., M.D., President of ASCO, Ballve-Lantero Professor of Oncology and professor of pathology and laboratory medicine at the Indiana University School of Medicine.

“With our growing understanding of the nature of cancer development and behavior, cancer is becoming a chronic disease that a growing number of patients can live with for many years,” said Dr. Sledge. “The studies released today are the latest examples of progress against the disease, from new personalized treatments, to new approaches to screening and prevention.”

The study results from a large clinical trial involving ovarian cancer screening were highlighted in today’s press briefing as summarized below.

Screening with CA-125 and Transvaginal Ultrasound Does Not Reduce Ovarian Cancer Death Rate, Results in High Number of False Positives

A randomized, multicenter screening study of nearly 80,000 women in the general population showed that using a CA-125 blood test and transvaginal ultrasound for early detection of ovarian cancer did not reduce the risk of dying from the disease, and resulted in a large number of false positives and related biopsies and follow-up procedures. The results indicate that while these tests are widely and appropriately used to evaluate symptoms, and to gauge disease status and effectiveness of treatment in women already diagnosed with ovarian cancer, they are not useful in screening the general population.

Saundra S. Buys, M.D., Medical Director, Huntsman Cancer Institute’s High Risk Breast Cancer Clinic; Professor, Depart. of Internal Medicine, Univ. of Utah School of Medicine

“There hasn’t been a good method for the early detection of ovarian cancer, and our hypothesis was that CA-125 and transvaginal ultrasound, which are useful in measuring disease, would also identify ovarian cancer early, at a stage in which it is more likely to be cured,” said lead author Saundra Buys, M.D., professor of medicine at the University of Utah and Huntsman Cancer Institute in Salt Lake City. “The results were disappointing, but not necessarily surprising. The study shows that the available tests are not effective and may actually cause harm because of the high number of false positives. These results point to the continued need for more precise and effective screening tools for this disease.”

In the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, 78,216 women ages 55 to 74 were assigned to either annual screening (39,105 women) or usual care (39,111 women) between 1993 and 2001. Women in the screening arm were offered annual CA-125 testing for six years and transvaginal ultrasound for four, and followed for up to 13 years. Those in the usual care arm were not offered the screening tests.

The results showed no statistically significant difference in ovarian cancer cases or mortality between the two arms. Ovarian cancer was diagnosed in 212 women in the screening group arm compared to 176 in the usual care arm; 118 women in the screening arm died from ovarian cancer, while 100 died from ovarian cancer in the usual care group.

Among women in the screening arm, there were a high number of false positives – 3,285 false positives, compared to just 212 true positives. Of women who had a false positive test, 1,080 underwent surgery for biopsy – the procedure generally required to evaluate positive test results; 163 of them had serious complications.

The authors emphasized that the study results don’t apply to screening women with symptoms or abnormal findings on physical examination. [emphasis added] Physical examination based on symptoms and appropriate follow-up testing remains the best available approach for ovarian cancer detection.

[Note: This summary contains updated data and a correction from the original abstract. Correction:  Of the 3,285 women who received a false positive exam, 1,080 underwent surgery. Of those surgical patients, 163 encountered at least one serious complication.]

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2011 ASCO Annual Meeting Abstracts (Including Ovarian Cancer) Made Publicly Available Today

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More than 30,000 cancer specialists from around the world will gather at the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting to discuss the latest innovations in research, quality, practice and technology in cancer.

More than 30,000 cancer specialists from around the world will gather at the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting to discuss the latest innovations in research, quality, practice and technology in cancer.

The meeting will be held June 3-7, 2011 at McCormick Place located in Chicago, Illinois. This meeting will be the platform for the release of thousands of scientific abstracts — highly anticipated research news for many people, including patients, caregivers, and the general public. Today, many of those abstracts were made publicly available online (see below).

The 2011 Annual Meeting will center on a theme of “Patients, Pathways, Progress.” The theme, which was selected by ASCO President George W. Sledge, Jr., M.D., promises to:

  • Represent “patients first,” said Dr. Sledge. “Everything we do as a Society has, as its eventual goal, the reduction of cancer mortality and morbidity. We’re on the front line in the war against cancer.”
  • Focus on the molecular, clinical and research pathways that are used to find, develop and implement new treatments for people living with cancer.
  • Celebrate the progress that has already been made in the treatment of cancer, while also reaffirming ASCO’s commitment to aggressive advancements in cancer research in the future.
News announced during the Annual Meeting will include the latest findings from cancer clinical trials, including new drug studies that could change current standards of care. ASCO shares this timely information with the public in a variety of ways. Free patient-friendly summaries of research news highlights from this year’s Annual Meeting will be available via ASCO’s patient information website, Cancer.Net (www.cancer.net). Cancer.Net will post scientific news as soon as it becomes publicly available, on both its homepage and its ASCO Annual Meetings section. The offerings on Cancer.Net include:
  • Easy-to-read summaries that put the top scientific news into context for patients.
  • Videos and podcasts of national and international cancer experts, breaking down the science into specific disease areas and explaining what the studies mean for people with cancer.
  • A news archive from previous ASCO Annual Meetings, which is searchable by year or disease type.

To receive ASCO Annual Meeting breaking news via email, you can sign up now to receive special editions of the newsletter Inside Cancer.Net. You can also follow Cancer.Net on Facebook or Twitter, where real-time updates will also be posted.

Medical abstracts from this year’s meeting were released today at 6:00 P.M. EDT/3:00 P.M. PDT, and additional studies will be released each day of the event in June.

The abstract categories released today, which may be of interest to an ovarian cancer survivor, include the following:

Cancer Prevention/Epidemiology

Developmental Therapeutics – Clinical Pharmacology and Immunotherapy

Gynecologic Cancer