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

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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Related Libby’s H*O*P*E* Postings:

Caris Life Sciences Launches Molecular Profiling Service For Ovarian Cancer Patients

Caris Life Sciences announces the launch of a new molecular profiling service for ovarian cancer patients

Caris Life Sciences, Inc. (Caris), a leading biosciences company focused on enabling precise and personalized healthcare through the highest quality anatomic pathology, molecular profiling, and blood-based diagnostic services, announced the launch of a new, Caris Target Now™ molecular profile for ovarian cancer patients. This expansion of the Caris Target Now™ offering provides individualized molecular information to treating physicians, relevant to the selection of therapies to treat this highly-lethal cancer. Ovarian cancer affects more than 20,000 women annually and produces some of the highest five-year mortality rates found among the 200+ types of cancer.

Caris Target Now™ molecular profiling examines the unique genetic and molecular make-up of each patient’s tumor so that treatment options may be matched to each patient individually.  Caris Target Now™ helps patients and their treating physicians create a cancer treatment plan based on the tumor tested. By comparing the tumor’s information with data from published clinical studies by thousands of the world’s leading cancer researchers, Caris can help determine which treatments are likely to be most effective and, just as important, which treatments are likely to be ineffective.

The Caris Target Now™ test is performed after a cancer diagnosis has been established and the patient has exhausted standard of care therapies or if questions in therapeutic management exist. Using tumor samples obtained from a biopsy, the tumor is examined to identify biomarkers that may have an influence on therapy. Using this information, Caris Target Now™ provides valuable information on the drugs that will be more likely to produce a positive response. Caris Target Now™ can be used with any solid cancer such as lung cancer, breast cancer, prostate cancer, and now, ovarian cancer.

Evidence Behind Caris Target Now™

Daniel D. Von Hoff, M.D., F.A.C.P., is the Executive Director of Caris Life Sciences' Clinical Research

A multi-center, prospective, pilot study first published in The Journal of Clinical Oncology (JCO) in October 2010 [1] — along with an accompanying editorial [2] —  determined that personalized cancer treatment tailored to a tumor’s unique genetic make-up identified therapies that increased progression free survival (PFS) over previous therapies in 27% of patients with advanced disease.

The purpose of the study was to compare PFS using a treatment regimen based on the molecular profiling (MP) of a patient’s tumor with the PFS determined for the most recent regimen on which the patient had experienced progression after taking that regimen for 6 weeks.  Unlike a typical control study, each patient was his or her own study control.  Tissue samples from patients with refractory metastatic cancer were submitted for MP in two formats including:

In many of these refractory tumors, targets for conventional therapies were identified, which was “a surprise finding,” according to Dr. Daniel Von Hoff, the Executive Director of Caris’ Clinical Research.  But the profiling also suggested therapies in cases where the treating physician was unsure regarding the next line of treatment. The MP approach was found to have clinical benefit for the individual patient who had a PFS ratio (PFS on MP selected therapy/PFS on prior therapy) of ≥ 1.3.  Among the 86 patient tumors that were profiled with Caris Target Now™:

  • 84 (98%) had a detected molecular target;
  • 66 of the 84 patients were treated with therapies that were linked to their MP results; and
  • 18 (27%) of 66 patients had a PFS ratio of ≥ 1.3 (95% CI, 17% to 38% range; one-sided, one-sample P = .007).

The study investigators concluded that it is possible to identify molecular targets in patients’ tumors. In 27% of the patients, the MP approach resulted in a longer PFS on a MP-based regimen than on the regimen that was based on physician’s choice.  “It was also encouraging to see that the overall survival in these 18 patients was better than that for the whole group of 66 patients (9.7 vs. 5 months),” said Von Hoff.

Of the 66 participants, 27% had breast cancer, 17% had colorectal cancer, and 8% had ovarian cancer; the remainder were classified as miscellaneous.  The improvement in PFS among the various types of cancer patients was as follows: 44% in patients with breast cancer, 36% in those with colorectal cancer, 20% in those with ovarian cancer, and 16% in the miscellaneous group.

The investigators in the study utilized Caris Target Now™ molecular profiling, which is currently available to oncologists and their patients.

“Oncologists commonly expect a 1-in-20 chance of patient response in 3rd- and 4th-line therapies.  This recent study suggests those odds can be improved to 1-in-4 when using therapeutic guidance provided by Caris Target Now™.”

Dr. Jeff Edenfield, a practicing oncologist with US Oncology, and routine user of Caris Target Now™

Since 2008, more than 15,000 cancer patients have received a Caris Target Now™ molecular profile. Caris Target Now™ has been designed to provide treating physicians with therapeutic options, often identifying anti-tumor agents that may not have been considered before. The Caris Target Now™ report is based on the genetic make-up of an individual patient’s tumor cross-referenced with a vast and growing proprietary database of clinical literature, correlating genetic tumor information to therapeutic response. Using biomarker-based therapies has been linked to the likelihood of a positive patient response.

James H. Doroshow, M.D., Director, Division of Cancer Treatment & Diagnosis, National Cancer Institute

In the accompanying JCO editorial, James H. Doroshow, M.D., the Director of the National Cancer Institute (NCI) Division of Cancer Treatment and Diagnosis, commented that the study by Von Hoff et. al. possessed several limitations. [2] The stated limitations of the study include (i) uncertainty surrounding the achievement of the study’s primary end point based upon use of the time-to-disease progression (TTP) index; (ii) limited prior experience with patients as their own controls, and (iii) lack of study randomization.  Despite these limitations, Dr. Doroshow noted that important lessons can be learned from the study conducted by Von Hoff et. al.

“First and foremost, this study vividly reminds us that the need for therapeutic intervention arises one patient at a time. When we sit with an individual who is trying to live with an advanced solid tumor after having already received several different chemotherapy regimens, it is unlikely that any published prognostic index or gene signature, as currently implemented, will be of much help in decision making—for physicians or for patients. [citation omitted]. Thus, a truly urgent need exists to move past the empiric therapeutic paradigm that launched the first half century of systemic oncologic treatment. [citation omitted]. Von Hoff et al have taken a noteworthy, albeit somewhat flawed, first step in this direction in their attempt to imagine a novel paradigm for cancer therapy, using the techniques of molecular tumor characterization on an individual patient basis. Future investigators of new cancer therapies should learn from this initial effort and focus on how these rapidly evolving molecular tools can be used in the development of an entirely new investigative model for the systemic treatment of cancer.”

Caris is currently conducting and initiating additional studies of Caris Target Now™ molecular tumor profiling through collaboration with leading institutions and cancer centers. 

With 300% growth in utilization in 2010, medical oncologists are recognizing the utility and value of this novel approach in providing improved care to patients. Physician adoption is rapidly accelerating, as Caris recently reached the threshold of providing Caris Target Now™ services to more than 1,000 patients per month. This new introduction for ovarian cancer is most relevant for physicians treating women who have progressed on platinum-based therapy and/or who need guidance for third-line treatment options. Caris Target Now™ for ovarian cancer offers the opportunity for these women to benefit from personalized and targeted therapy guidance based upon molecular profiling.

“Ovarian cancer is a highly-lethal cancer that presents distinct diagnostic and therapeutic challenges, often presenting no major symptoms until the cancer has metastasized,” said Dr. Les Paul, Caris’ Senior Vice President for Medical Affairs. “Choosing the optimal therapeutic intervention at the earliest possible stage is critical to extending progression free survival in ovarian cancer patients. With the introduction of the Caris Target Now™ ovarian profile, we are able to support physicians with as much information as possible, including the latest relevant clinical literature citations to aid them in making the best therapeutic decision possible for each patient.”

Examples of the potential use of an existing clinical trial drug to target a specific molecular characteristic possessed by an ovarian cancer include:

Use of Molecular Profiling By Leading Medical Institutions; Sponsorship By A Charitable Foundation

It should be noted that molecular profiling is already being used in clinical practice at several leading cancer institutions.  At Massachusetts General Hospital, (MGH), The MGH Cancer Centre uses a PCR-based mutation-detection assay and state-of-the-art robotic technology, called “SNaPshot,” to look for 130 known gene mutations in tumor tissue. “We are already using molecular profiling for all our lung cancer patients,” said Jeffrey Settleman, Ph.D., scientific director at the MGH Cancer Center, to Medscape Oncology in 2009. [12] “This has already had an impact on treatment decisions, and it appears to be improving treatment. We have seen better response rates and we hope that this will translate into better survival.”  In fact, MGH is engaged currently in the largest study aimed at matching tumor genomes to potential anticancer treatments. [13] It is our understanding that MGH performs molecular profiling currently on melanoma, leukemia, brain and metastatic breast cancer, and metastatic adenocarcinoma that start in the lung, colon or rectum.

Several other institutions are in the process of developing or have developed their own systems, including the University of Texas M.D. Anderson Cancer Center [14], and the Dana-Farber Cancer Institute [15].  All are striving to profile individual tumors so that therapy can be personalized, which means that it has a better chance of working because it targets specific mutations found in a patient’s tumor. The MP approach also prevents patients from being exposed to drugs that have a limited chance of success, eliminating toxicity and improving quality of life.

We should also note the Clearity Foundation sponsors molecular profiling services on behalf of ovarian cancer patients at no cost. The Clearity Foundation is a 501(c)(3) not-for-profit, founded by Laura Shawver, Ph.D., who is an ovarian cancer survivor and research scientist.  The Clearity Foundation seeks to improve treatment outcomes in recurrent and progressive ovarian cancer patients by providing diagnostic services that determine the molecular profile of the individual patient with the belief that a molecular “blueprint” is crucial to finding appropriate treatments.

About Caris Target Now™

Caris Target Now™ is a comprehensive tumor analysis coupled with an exhaustive clinical literature search, which matches appropriate therapies to patient-specific biomarker information to generate an evidence-based treatment approach. Caris Target Now™ testing provides information that may help when considering potential treatment options.

Caris Target Now™ begins with an immunohistochemistry (IHC) analysis. An IHC test measures the level of important proteins in cancer cells providing clues about which therapies are likely to have clinical benefit and then what additional tests should be run.

If there is access to a frozen sample of patient tissue available, Caris may also run a gene expression analysis by microarray. The microarray test looks for genes in the tumor that are associated with specific treatment options.

As deemed appropriate based on each patient, Caris will run additional tests. Fluorescent In-Situ Hybridization (FISH) is used to examine gene copy number variation (i.e., gene amplification) in the tumor. Polymerase Chain Reaction (PCR) or DNA sequencing is used to determine gene mutations in the tumor DNA.

Caris takes the results from each test and applies the published findings from thousands of the world’s leading cancer researchers. Based on this analysis, Caris Target Now™ identifies potential therapies for patients and their treating physicians to discuss.

Caris Target Now™ was developed and its performance characteristics were determined by Caris, a CLIA-certified medical laboratory in compliance with the U.S. Clinical Laboratory Amendment Act of 1988 and all relevant U.S. state regulations. It has not been approved by the United States Food and Drug Administration.

About Caris Life Sciences

Caris Life Sciences, a leading biosciences company, specializes in the development and commercialization of the highest quality anatomic pathology, molecular profiling, and blood-based diagnostic technologies, in the fields of oncology, dermatopathology, hematopathology, gastrointestinal pathology and urologic pathology. The company provides academic-caliber consultations for patients every day, through its industry-leading team of expert, subspecialty pathologists. Caris also offers advanced molecular analyses of patient samples through prognostic testing services and genomic, transcriptomic, and proteomic profiling to assist physicians in their treatment of cancer. Currently, Caris is developing the Carisome™ platform, a proprietary, blood-based technology for diagnosis, prognosis, and theranosis of cancer and other complex diseases. The company is headquartered in the Dallas metroplex, and operates laboratories at the headquarters, as well as in the Phoenix and Boston metro areas.

About Daniel Von Hoff, M.D., FACP, Executive Director, Caris Life Sciences Clinical Research

Daniel D. Von Hoff, M.D., is currently physician-in-chief and director of translational research at Translational Genomics Research Institute (TGen) in Phoenix, Arizona. He is also chief scientific officer for US Oncology and the Scottsdale Healthcare’s Clinical Research Institute.  He holds an appointment as clinical professor of medicine at the University of Arizona College of Medicine.

Dr. Von Hoff’s major interest is in the development of new anticancer agents, both in the clinic and in the laboratory. He and his colleagues were involved in the beginning of the development of many of the agents now in routine use, including: mitoxantrone, fludarabine, paclitaxel, docetaxel, gemcitabine, irinotecan, nelarabine, capecitabine, lapatinib and others.

At present, Von Hoff and his colleagues are concentrating on the development of molecularly targeted therapies particularly for patients with advanced pancreatic cancer. Dr. Von Hoff’s laboratory interests and contributions have been in the area of in vitro drug sensitivity testing to individualize treatment for the patient, mechanisms of gene amplification, particularly of extrachromosomal DNA, and understanding of and targeting telomere maintenance mechanisms. His laboratory work now concentrates on the discovery of new targets in pancreatic cancer.

Dr. Von Hoff has published more than 543 papers, 133 book chapters, and more than 956 abstracts. Dr. Von Hoff  also served on President Bush’s National Cancer Advisory Board from June 2004 through March 2010.

Dr. Von Hoff is the past president of the American Association for Cancer Research(AACR) (the world’s largest cancer research organization), a fellow of the American College of Physicians, and a member and past board member of the American Society of Clinical Oncology (ASCO). He is a founder of ILEX™ Oncology, Inc. (acquired by Genzyme after Ilex had 2 agents, alemtuzumab and clofarabine approved for patients with leukemia). He is founder and the editor emeritus of Investigational New Drugs – The Journal of New Anticancer Agents; and, editor-in-chief of Molecular Cancer Therapeutics. He is also proud to have been a mentor and teacher for multiple medical students, medical oncology fellows, graduate students, and post-doctoral fellows. He is a co-founder of the AACR/ASCO Methods in Clinical Cancer Research Workshop.

References:

1/ Von Hoff DD, Stephenson JJ Jr, Rosen P, et. al. Pilot study using molecular profiling of patients’ tumors to find potential targets and select treatments for their refractory cancers. J Clin Oncol. 2010 Nov 20;28(33):4877-83. Epub 2010 Oct 4. PubMed PMID: 20921468.

2/ Doroshow JH. Selecting systemic cancer therapy one patient at a time: Is there a role for molecular profiling of individual patients with advanced solid tumors? J Clin Oncol. 2010 Nov 20; 28(33):4869-71. Epub 2010 Oct 4. PMID: 20921466.

3/Addition of Dasatinib (Sprycel) to Standard Chemo Cocktail May Enhance Effect in Certain Ovarian Cancers, by Paul Cacciatore, Libby’s H*O*P*E*™, April 19, 2009.

4/UCLA Researchers Significantly Inhibit Growth of Ovarian Cancer Cell Lines With FDA-Approved Leukemia Drug Dasatinib (Sprycel®), by Paul Cacciatore, Libby’s H*O*P*E*™, November 11, 2009.

5/BMS-345541 + Dasatinib Resensitizes Carboplatin-Resistant, Recurrent Ovarian Cancer Cells, by Paul Cacciatore, Libby’s H*O*P*E*™, July 1, 2010.

6/PARP Inhibitor Olaparib Benefits Women With Inherited Ovarian Cancer Based Upon Platinum Drug Sensitivity, by Paul Cacciatore, Libby’s H*O*P*E*™, April 23, 2010.

7/ Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriersN Engl J Med. 2009 Jul 9;361(2):123-34. Epub 2009 Jun 24. PMID: 19553641.

8/Audeh MW, Penson RT, Friedlander M, et al. Phase II trial of the oral PARP inhibitor olaparib (AZD2281) in BRCA-deficient advanced ovarian cancer. J Clin Oncol 2009;27(supplement):p. 15S.

9/PARP Inhibitor MK-4827 Shows Anti-Tumor Activity in First Human Clinical Study, by Paul Cacciatore, Libby’s H*O*P*E*™,  November 17, 2010.

10/PI3K Pathway: A Potential Ovarian Cancer Therapeutic Target?, by Paul Cacciatore, Libby’s H*O*P*E*™,  November 20, 2009.

11/Endocyte’s EC145 Produces Significant Anti-Tumor Activity In Advanced Stage Chemoresistant Ovarian Cancer Patients, by Paul Cacciatore, Libby’s H*O*P*E*™, October 21, 2009.

12/Massachusetts General Hospital Cancer Center To Genetically Profile All Patient Tumors, by Paul Cacciatore, Libby’s H*O*P*E*™, March 14, 2009.

13/Largest Study Matching Genomes To Potential Anticancer Treatments Releases Initial Results, by Paul Cacciatore, Libby’s H*O*P*E*™, August 3, 2010.

14/An Initiative for Molecular Profiling in Advanced Cancer Therapy (IMPACT) Trial. A Molecular Profile-Based Study in Patients With Advanced Cancer Treated in the Investigational Cancer Therapeutics Program, University of Texas M.D. Anderson Cancer Center, ClinicalTrials.gov Identifier: NCT00851032.

15/Dana-Farber Researchers “OncoMap” The Way To Personalized Treatment For Ovarian Cancer, by Paul Cacciatore, Libby’s H*O*P*E*™, November 16, 2010.

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Additional Information:

Personalized Medicine Helps Breast, Colorectal & Ovarian Cancer Patients Survive

“Cancer patients can survive longer under treatments based on their individual genetic profiles, according to a nationwide study released jointly today by Phoenix-area healthcare organizations. The study shows that molecular profiling of patients can identify specific treatments for individuals, helping keep their cancer in check for significantly longer periods, and in some cases even shrinking tumors. Study results were released today at the 100th annual meeting of the American Association for Cancer Research in Denver by Dr. Daniel Von Hoff, Physician-In-Chief of the Phoenix-based Translational Genomics Research Institute (TGen), and the study’s Principal Investigator. … Patients experienced varying levels of improvement. Among those with breast cancer, the period of progression-free survival increased for 44 percent of patients; for colorectal, 36 percent of patients; for ovarian, 20 percent of patients; and for miscellaneous cancers the improvement was seen in 16 percent of patients. …” [Emphasis added by Libby’s H*O*P*E*™]


tgen-logo1

“Personalized medicine helps cancer patients survive – TGen, Scottsdale Healthcare and Caris Dx clinical trial shows molecular profiling can result in specific treatments for individual patients that significantly limit the growth and spread of tumors

PHOENIX, Ariz. – April 19, 2009 – Cancer patients can survive longer under treatments based on their individual genetic profiles, according to a nationwide study released jointly today by Phoenix-area healthcare organizations.

The study shows that molecular profiling of patients can identify specific treatments for individuals, helping keep their cancer in check for significantly longer periods, and in some cases even shrinking tumors.

von_hoff

Daniel Von Hoff, M.D., F.A.C.P., Physician in Chief & Senior Investigator, The Translational Genomics Research Institute; Chief Scientific Officer, TGen Clinical Research Services, Scottsdale Healthcare; Clinical Professor of Medicine, University of Arizona Department of Medicine

Study results were released today at the 100th annual meeting of the American Association for Cancer Research in Denver by Dr. Daniel Von Hoff, Physician-In-Chief of the Phoenix-based Translational Genomics Research Institute (TGen), and the study’s Principal Investigator.

The study included 66 patients at nine centers across the United States, including Scottsdale Heathcare. Dr. Von Hoff also is the Chief Scientific Officer of TGen Clinical Research Services (TCRS) at Scottsdale Healthcare, a partnership between TGen and Scottsdale Healthcare that is administered by the Scottsdale Clinical Research Institute (SCRI) at Scottsdale Healthcare.

All of the patients had previously experienced growth of their tumors while undergoing as many as two to six prior cancer treatments, including conventional chemotherapy.

However, after molecular profiling identified precise targets, new treatments were administered that resulted in patients experiencing significant periods of time when there was no progression of their cancer.

This clinical trial was unique because patients acted as their own control,’ said Dr. Von Hoff. ‘We compared each patient’s progression-free survival, following treatment based on molecular profiling, to how their tumors progressed under their prior treatment regimens, before molecular profiling.’

In a significant number of patients, the targeted treatments provided significantly longer periods when tumors did not progress, or even shrunk, said Dr. Von Hoff, who also is a Medical Director of US Oncology and a former Director of the Arizona Cancer Center at the University of Arizona.

Dr. Von Hoff said the new study was done in a way that avoided issues surrounding tumor subtypes and differences in individual biology, which have confounded other clinical trials.

He said this clinical trial demonstrated the value of personalized medicine, in which treatments are prescribed based on an individual’s specific genetic makeup. The type of drugs, dosages, their delivery and other treatment aspects – all are based on each patient’s individual medical needs.

Among the patients, 27 percent had breast cancer, 17 percent had colorectal cancer, 8 percent had ovarian cancer and 48 percent had cancers that were classified as miscellaneous.

Patients experienced varying levels of improvement. Among those with breast cancer, the period of progression-free survival increased for 44 percent of patients; for colorectal, 36 percent of patients; for ovarian, 20 percent of patients; and for miscellaneous cancers the improvement was seen in 16 percent of patients.

‘With this trial, we are showing the power of personalized medicine using the tools we already have available to us. As these tools become more precise and more effective, the value of personalized medicine will increase,’ Dr. Von Hoff said.

The molecular profiling for this research study was performed by Caris Diagnostics (Caris Dx) in Phoenix.

These results are the first in a series of studies in support of Target NowTM, a commercially-available oncology testing service offered exclusively by Caris Dx. Target Now uses cutting-edge molecular profiling techniques, including both DNA microarray and immunohistochemical (IHC) analysis, to provide individualized information about a patient’s tumor as an aid to the treating oncologist.

‘This trial is evidence of an important breakthrough in the treatment of cancer. We are excited to work with Dr. Von Hoff and TGen as we make this important molecular diagnostic information available to physicians to aid in therapy-selection decision making,’ said David D. Halbert, Chairman and CEO of Caris Diagnostics. ‘The valuable information provided through the Target Now panel of tests improves patient care while reducing costs for the payer.’

Clinical studies were conducted by TCRS at the Virginia G. Piper Cancer Center at Scottsdale Healthcare Shea Medical Center. Scottsdale Healthcare is a primary clinical research site for TGen.

‘Patients in our community have access to ground-breaking, world-class research right in their own backyard thanks to this collaboration,’ said Tom Sadvary, president and CEO of Scottsdale Healthcare. ‘Our goal is reducing the time it takes to get new treatment discoveries from the research lab to the patient. We are thrilled to see these advances in personalized medicine taking place right here in Scottsdale.’

The recent clinical study was dubbed the Bisgrove Trial, after longtime Scottsdale Healthcare supporter Jerry Bisgrove. The trial was funded through a $5 million grant from Mr. Bisgrove’s Stardust Foundation to the Scottsdale Healthcare Foundation. Mr. Bisgrove has been a patient at Scottsdale Healthcare and is a member of the Scottsdale Healthcare Foundation Board of Trustees. In honor of the Stardust gift, the research building at the Virginia G. Piper Cancer Center at Scottsdale Healthcare Shea Medical Center is named the Debi and Jerry Bisgrove Research Pavilion.

‘The Stardust Foundation is proud to have played a key role in the advancements in cancer research represented by Dr. Von Hoff’s clinical trial. We believe we are closer than ever to finding a cure for this devastating disease that affects so many millions,’ Mr. Bisgrove said.

*          *          *

About Scottsdale Healthcare
Scottsdale Healthcare is a primary clinical research site for TGen. TGen Clinical Research Services (TCRS) at Scottsdale Healthcare is housed in the Virginia G. Piper Cancer Center at Scottsdale Healthcare, located on the Scottsdale Healthcare Shea medical campus. Scottsdale Healthcare is the not-for-profit parent organization of the Scottsdale Healthcare Shea, Scottsdale Healthcare Osborn and Scottsdale Healthcare Thompson Peak hospitals, Virginia G. Piper Cancer Center, Scottsdale Clinical Research Institute, TGen Clinical Research Services at Scottsdale Healthcare, Scottsdale Healthcare Home Health Services, Scottsdale Healthcare Community Health Services, and Scottsdale Healthcare Foundation. For additional information, visit www.shc.org.

About Scottsdale Clinical Research Institute (SCRI)
SCRI, established in 2005, provides infrastructure and support for the clinical research at Scottsdale Healthcare. Start-up funding for SCRI was provided by a lead gift of $4.5 million from the Virginia G. Piper Charitable Trust in 2005. An additional $5 million was provided by the Stardust Foundation to support this multi-site molecular profiling study of targeted therapies for treatment refractory cancers coordinated by SCRI. A defining feature of SCRI is a focus on genomics and personalized medicine as well as clinical and translational research. The basic science arm of SCRI is provided by a partnership with the Translational Genomics Research Institute (TGen). Innovations from TGen’s laboratory are taken to the bedside at SHC by our joint clinical research program, TGen Clinical Research Services (TCRS) at Scottsdale Healthcare. Additional research collaborations include the University of Arizona, Arizona State University, other local health care delivery systems and participation in the Arizona NIH Clinical and Translational Science Award (CTSA) program initiative. Areas of study at SCRI include Cancer, Cardiovascular, Trauma, Metabolic and Nanomedicine.

Press Contact:
Keith Jones
Public Relations Director
Scottsdale Healthcare
480-882-4412
kjones@shc.org

About TGen
The Translational Genomics Research Institute (TGen) is a non-profit organization dedicated to conducting groundbreaking research with life changing results. Research at TGen is focused on helping patients with diseases such as cancer, neurological disorders and diabetes. TGen is on the cutting edge of translational research where investigators are able to unravel the genetic components of common and complex diseases. Working with collaborators in the scientific and medical communities, TGen believes it can make a substantial contribution to the efficiency and effectiveness of the translational process. For more information, visit: www.tgen.org.

Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
syozwiak@tgen.org

About Caris Diagnostics
Caris Diagnostics (Caris Dx) is a leading provider of the highest quality diagnostic, translational development and pharmaceutical services encompassing anatomic pathology and molecular testing. Caris Diagnostics provides world-class pathology services to physicians who treat patients in the community setting. The company provides academic-caliber medical consults through its industry-leading team of subspecialty fellowship and expert-trained pathologists in gastrointestinal and liver pathology, dermatopathology and hematopathology. Caris Diagnostics provides the highest levels of service to its customers and their patients through its state-of-the-art laboratories; proprietary, advanced clinical and technology solutions; and rigorous quality assurance programs. Through the molecular testing expertise of the Caris Molecular Profiling Institute (Caris MPI) at Caris Dx, the company also offers advanced molecular analyses of patient samples through prognostic testing services and genomic and proteomic profiling to provide critical information to physicians treating cancer and other complex diseases. In addition, Caris MPI supports pharmaceutical companies and other researchers in their clinical trials for targeted therapeutics with custom genomic and proteomic analyses, analyte preservation, tissue procurement and comprehensive reporting services. The company has strategic relationships with the International Genomics Consortium, US Oncology, the Translational Genomics Research Institute, and the Biodesign Institute of Arizona State University. More than 2,000 physicians nationally use Caris Diagnostics. Formed in 1996, the company is headquartered in Irving, Texas and operates four laboratories: Irving, Texas; Phoenix, Arizona (2 sites); Newton, Massachusetts. Additional information is available at www.carisdx.com.

Press Contact:
Brian Wright
Caris Dx
(602) 358-8916
bwright@carismpi.com”

Sources:

Massachusetts General Hospital Cancer Center To Genetically Profile All Patient Tumors

“The Massachusetts General Hospital Cancer Center has recently opened a new Translational Research Laboratory that will uncover the genetic codes and gene mutations from almost all of its cancer patients. … By embarking on such an ambitious approach, Cancer Center pathologists and oncologists hope to gather specific information about tumor properties that will lead to targeted therapies and better personalized treatments. Mass General will be the first and only cancer center to conduct molecular profiling of positive biopsies and tumors from all patients as part of basic patient care. …”

Genetic profiling

09/Mar/2009

massgenlab

Massachusetts General Hospital Cancer Center Opens Molecular Pathology Lab to Genetically Profile All Patient Tumors

The Massachusetts General Hospital Cancer Center has recently opened a new Translational Research Laboratory that will uncover the genetic codes and gene mutations from almost all of its cancer patients. Previously only a sampling of patients had their tumors analyzed in such a comprehensive fashion.

By embarking on such an ambitious approach, Cancer Center pathologists and oncologists hope to gather specific information about tumor properties that will lead to targeted therapies and better personalized treatments. Mass General will be the first and only cancer center to conduct molecular profiling of positive biopsies and tumors from all patients as part of basic patient care.

Scientists and researchers have already identified over 110 genetic mutations responsible for causing tumor growth, many of which are involved in several different types of cancers. Codirectors of the Transplational Research Laboratory, Leif Ellisen, MD, PhD, and A. John Iafrate, MD, PhD, have equipped the lab with state-of-the-art robotic technology, which will make it possible to quickly genotype tumor specimens within a short period of time.

‘This new and improved classification of cancers that we are doing is intended to give our oncologists more information about a individual patient’s cancer, so they can treat it in a very specific way, thereby significantly increasing the odds of success,’ says Iafrate.

Several new cancer drugs that are currently available or in development are able to block some of the mutations and pathways that cause tumor cells to proliferate. By targeting tumor gene mutations with these smart drugs, doctors may be able to eradicate malignant cells without using traditional treatments like chemotherapy and radiation, which have significant side effects.

The lab’s new tumor genotyping initiative should also expedite the time it takes to find the right drug for the right patient. According to Ellisen, ‘If we are able to identify a mutation in, say, a case of lung cancer, and we know that a particular drug has been successful in treating colon cancer patients with the same mutation, then we have good reason to believe that drug will work turning off the cancer-causing mutation in the lung cancer patient as well.’

The lab will start with the genotyping of Mass General’s lung cancer patients and phase in different disease groups over the next few weeks. It is anticipated that the profiling of all possible patient tumors will occur gradually over the coming months.

Learn more about research at the Cancer Center

Cited SourceMassachusetts General Hospital Cancer Center opens molecular pathology lab to genetically profile all patient tumors, News, Massachusetts General Hospital, Mar. 9, 2009.

Update:

  • Making Personalized Cancer Care Routine, In Depth, NCI Cancer Bulletin, Volume 6 / Number 11, National Cancer Institute, June 2, 2009 (noting that Massachusetts General Hospital & Memorial Sloan-Kettering Cancer Center are performing genetic profiling of all lung cancer tumors).