“The study included 2,000 consecutive patients with advanced cancer who underwent testing in a genomic testing protocol. Standardized hotspot mutation analysis was performed using either an 11-gene (251 patients) or a 46- or 50-gene (1,749 patients) multiplex platform. A total of 35 genes were considered potentially actionable, given the potential to be targeted with approved or investigational therapies.
“In total, 789 patients (39%) had at least one mutation in potentially actionable genes. Of them, 83 (11%) were enrolled in genotype-matched trials targeting these alterations. Among 230 patients with PIK3CA/AKT1/PTEN/BRAF mutations who returned for therapy, 116 (50%) received a genotype-matched drug; of them, 40 (17%) were treated in a genotype-selected trial requiring a mutation for eligibility, 16 (7%) were treated in a genotype-relevant trial targeting a genomic alteration without biomarker selection, and 40 (17%) received a genotype-relevant drug off trial.”
“Mutations in ARID1a, which are common in many cancer types, disrupt DNA damage repair in cancer cells, allowing the cancer to progress. This gene may also be an Achilles’ heel when treating certain tumors, according to a team of researchers at The University of Texas MD Anderson Cancer Center.
“The study, published in Cancer Discovery, discovered that certain mutations in ARID1a (AT-rich interactive domain-containing protein 1a), a gene recently implicated in cancer progression, sensitize some tumors to PARP inhibitor drugs, such as olaparib, veliparib and BMN673, which block DNA damage repair pathways.
” ‘Our results showed, particularly in the ARID1a deficient cells, PARP inhibitors are more effective than in other cancer cells,’ says Guang Peng, M.D., Ph.D, assistant professor, Clinical Cancer Prevention, and senior author of the study. ‘Based on the mechanism we’ve discovered, we propose a new approach for targeting these mutant cancer cells.’ ”
“Much of precision medicine and cancer care focuses on targeting the genomes of specific tumors or metastases. A Weill Cornell Medical College research team has now shown that a more global look at the body using next-generation sequencing can offer new insights and treatment targets in patients with advanced, treatment-resistant disease.
“The research, published May 28 in JAMA Oncology, offers a look at how the Institute for Precision Medicine at Weill Cornell and NewYork-Presbyterian Hospital is transforming the way physician-scientists address individualized cancer care.
” ‘Most institutions are using focused or panel sequencing to look at a few hot spot mutation areas in cancer,’ said senior author Dr. Mark Rubin, the institute’s director, and the Homer T. Hirst III Professor of Oncology in Pathology and a professor of pathology and laboratory medicine at Weill Cornell. ‘But we believe that Whole Exome Sequencing, which tests more than 21,000 genes in the cancer’s exome, the DNA that is transcribed into RNA, is ideal for patients with advanced cancer where we don’t know where the mutations of resistance are.’ “
“The German Breast Group (GBG) presented two analyses that can serve as predictors of response to treatment by further subdividing preoperative (neoadjuvant) patients with HER 2 positive breast cancer and those with triple negative breast cancer based on tumor DNA repair capabilities and related factors.
“Prof. Dr. Gunter von Minckwitz, president of the GBG Research Institute, noted, ‘Taken together these studies demonstrate that a deeper understanding of the variations among breast cancer types that go beyond hormone response and BRCA gene mutations can inform treatment options with increased precision.’
“One study (Abstract No: 1004) fromlead author Dr. von Minckwitz found cancer-related BRCA mutations in the tumor are more common (30.3%) than inherited BRCA mutations (19.8%) in patients with triple-negative breast cancer. The homologous recombination (HR) assay measures DNA repair capacity beyond those related to BRCA mutation. HR deficiency defined as having either a BRCA mutation of the tumor or a high HR score was found in 70.5% of the patients. These findings can affect treatment options. Patients with a tumor BRCA mutation and/or a high HR score showed a high complete response to preoperative (neoadjuvant) chemotherapy. Our findings suggest those patients are also benefiting more from the additional use of carboplatin than tumors without HR deficiency.”
“Biodesix, Inc. today announced the launch of GeneStrat™, a targeted liquid biopsy mutation test for genotyping tumors of patients with advanced non-small cell lung cancer (NSCLC). The blood test results are available within 72 hours, providing physicians actionable diagnostic information prior to making treatment decisions. GeneStrat is focused exclusively on the clinically actionable EGFR, KRAS, and BRAF mutations often used to guide targeted therapy treatment decisions. GeneStrat also captures the EGFR T790M mutation, which can be used for monitoring the emergence of the primary resistance mutation in the EGFR gene. It is anticipated that two drugs targeting the resistance mutation may be available later this year. GeneStrat uses the ddPCR platform to analyze cell-free tumor DNA and is highly concordant with tissue analysis, currently considered the gold standard.
“Roughly 30% of lung cancer patients either have insufficient biopsy tissue or are not candidates for a biopsy for tumor mutation profiling. Even in cases where tissue biopsy is available, the sense of urgency to treat is great, with one recent study showing that one out of four patients begin cancer treatment before receiving mutation test results. Requiring only a blood draw, GeneStrat offers a fast, minimally invasive alternative to a high-risk tissue biopsy or re-biopsy in patients with insufficient tissue.
“In addition to providing a minimally-invasive source of mutation status, liquid biopsy can be more cost-effective than traditional tissue biopsies. The mean cost of each tissue biopsy is $14,634 across all patients. The cost of a tissue biopsy can be up to four time higher in the 19.3% of patients who have complications associated with the biopsy. GeneStrat liquid biopsy can help avoid the cost and complications of repeat tissue biopsy.”
“The American Society of Clinical Oncology (ASCO) today announced its first-ever clinical trial that will offer patients with advanced cancer access to molecularly-targeted cancer drugs and collect ‘real-world’ data on clinical outcomes to help learn the best uses of these drugs outside of indications approved by the Food and Drug Administration (FDA). Plans for the Targeted Agent and Profiling Utilization Registry (TAPUR) study, including the participation of major pharmaceutical companies that will contribute free drugs, were released in a news briefing at the Society’s 2015 Annual Meeting in Chicago.
“The ASCO-sponsored prospective, non-randomized clinical trial will collect information on the anti-tumor activity and toxicity of commercially available, targeted cancer drugs in a range of cancer types, including any advanced solid tumor, multiple myeloma, or non-Hodgkin lymphoma with a genomic variation known to be a drug target.
“ ‘Oncologists often use therapies approved for a specific cancer indication to treat people with other types of advanced cancer, but we very rarely learn from that experience to benefit other patients,’ said ASCO President Peter Paul Yu, MD, FACP, FASCO. ‘TAPUR will document the real-world experience of patients who receive commercially available targeted anti-cancer drugs and will describe the effectiveness and side effects of a range of targeted agents available in this study.’ “
“The federal government is launching a very different kind of cancer study that will assign patients drugs based on what genes drive their tumors rather than the type.
“The National Cancer Institute’s NCI-MATCH trial will be a massive precision medicine experiment at more than 2,400 sites around the country.
“Starting in July, about 3,000 patients will have their tumor genes sequenced to see what mutations or pathways fuel their disease. About 1,000 patients whose tumor characteristics most closely match one of the 20 or so gene-targeting drugs offered in the study will be put into groups of about 30 patients to get that drug.
” ‘The goal is really to try to get the information faster, so when we see responses we can expand rapidly’ and offer the drug more widely, said Dr. Douglas Lowy, the Cancer Institute’s acting director.”
“Drugmakers including Bristol-Myers Squibb Co and Merck & Co are testing which patients will most benefit from new cancer treatments based on a protein found in their tumors, but that guide, known as a biomarker, may be too unreliable, researchers and health experts said.
“Bristol’s Opdivo and Merck’s Keytruda are both therapies designed to block a protein known as Programmed Death receptor (PD-1) that tumors use to evade the body’s natural defenses. Competitors Roche Holding, AstraZeneca and Pfizer also have similar drugs in an earlier stage of development. The drugmakers are conducting clinical trials that test patient tumors for a related protein called PD-L1.
“The new drugs are mainly aimed at patients with so-called solid tumors suffering from diseases including lung cancer and liver cancer. Lung cancer, the most common type, claims 1.8 million new cases each year worldwide. Sales of drugs to block PD-1 could reach $33 billion a year by 2022, according to Morningstar.”
“Although 90 percent of women with early-stage breast cancer said they were aware they took a genomic test that identified their level of risk for a recurrence of the disease, one in five didn’t know the results of that analysis, according to a new fact sheet by the UCLA Center for Health Policy Research.
“The test, called gene expression profiling, or GEP, is used by physicians to help guide treatment decisions and can potentially help people avoid unnecessary chemotherapy. One of a number of emerging ‘precision medicine’ genomic technologies, the GEP estimates the activity of specific genes in breast cancer cells, which can help predict whether there is a greater chance for breast cancer to return. Those with a high risk for cancer growth benefit by having chemotherapy as part of their treatment, the authors write, but chemo has no added value for those with a low risk.”