“HER2 and hormone-receptor status should form the basis for biomarker testing in metastatic breast cancer, according to a new clinical practice guideline from the American Society of Clinical Oncology (ASCO).
“All patients with accessible metastases should have biopsies to determine disease status. Retesting of HER2, estrogen receptor, and progesterone status should be offered, although data are insufficient to know whether a change in therapy based on the markers’ status will affect outcomes.
“In the case of discordant findings from biopsies of primary tumors and metastases, the marker status of the metastasis should take precedence with respect to treatment decisions, Catherine Van Poznak, MD, of the University of Michigan in Ann Arbor, and colleagues advised in a statement published online in the Journal of Clinical Oncology. Tests for carcinoembryonic antigen (CEA), cancer antigen (CA) 15-3 and CA 27-29 may be used adjunctively but not by themselves.”
“The combination of lapatinib (Tykerb) and trastuzumab (Herceptin) is active and well-tolerated when given to patients with human epidermal growth factor receptor 2-positive (HER2) metastatic breast cancer (MBC) who have received up to two lines of therapy for advanced disease, a nonrandomized phase II study now shows.
“What’s more, early metabolic imaging by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) appears to provide the key to selecting patients who can be treated with targeted regimens and spared the toxicity of chemotherapy, Nancy U. Lin, MD, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, Boston, Ma., and colleagues report online in the Journal of Clinical Oncology.
” ‘Because the number of treatment options and their cost for patients with HER2-positive breast cancer continues to increase, a key question is how best to tailor therapies to individual patients,’ said Lin. ‘In the metastatic setting, predictive tests for clinical benefit could spare patients unnecessary toxicity and cost from ineffective therapies and maximize the likelihood of meaningful improvements from treatment. In the early-stage setting, predictive tests may reduce both under- and overtreatment.’ “
“Iressa (gefitinib) has been approved by the U.S. Food and Drug Administration to treat patients with metastatic non-small-cell lung cancer (NSCLC) with a specific genetic mutation (epidermal growth factor receptor [EGFR]). A just-approved companion diagnostic test can identify patients who could benefit from this new use.
“Iressa is a kinase inhibitor, a class of drugs designed to block proteins that spur development of cancer cells. The therascreen EGFR RGQ PCR Kit is a newly approved diagnostic that can help doctors detect patients with the genetic mutation who are candidates for treatment with Iressa.
“Iressa was evaluated for this use in clinical trials involving 106 people with previously untreated EGFR mutation-positive metastatic NSCLC. Tumors shrank in about 50 percent of people treated with Iressa 250 mg once daily. This effect lasted an average of six months, the FDA said. Severe side effects of Iressa may include interstitial lung disease, liver damage, gastrointestinal perforation, severe diarrhea, and ocular disorders. More common side effects are diarrhea and skin reactions.”
“Only a small percentage of patients with actionable gene alterations are eventually enrolled onto genotype-matched trials targeting these alterations, according to study results.
“With the influx of targeted molecular therapies for the treatment of cancer, genomic profiling and matching patients to targeted therapies are imperative, according to study background.
“ ‘However, implementation of genomically informed therapy requires not only access to genomic profiling, but also the availability of molecularly targeted therapies matched to the genomic testing results,’ Funda Meric-Bernstam, MD, chair of the department of investigational cancer therapeutics, at The University of Texas MD Anderson Cancer Center, and colleagues wrote. ‘Availability of clinical trials may not only differ from institution to institution, but may also differ between tumor types. Enrollment onto clinical trials is also limited by trial eligibility criteria, as well as availability of slots.’ ”
“Mayo Clinic and the Translational Genomics Research Institute (TGen) are helping launch a national clinical trial that will apply the latest in precision medicine to treat advanced melanoma skin cancer.
“The study leverages advances in genomics, informatics, and health information technology, yielding more precise medical treatments for patients with this devastating disease.
“Mayo Clinic is the only clinical site in Arizona to offer this new treatment, sponsored by Stand Up to Cancer (SU2C) and the Melanoma Research Alliance. These clinical trials are the culmination of nearly four years of research under an SU2C Melanoma Dream Team grant.
“Metastatic melanoma is a type of cancer that has spread from the skin to other parts of the body, most frequently the lungs, muscles, brain, and liver. Metastatic melanoma is responsible for more than 9,000 deaths a year in the United States, so there remains an urgent need for new treatment options.”
Earlier this year, a new treatment option was added to the arsenal for ER-positive breast cancer in postmenopausal women when the U.S. Food and Drug Administration (FDA) approved the combination of letrozole (Femara) and palbociclib (Ibrance). Continue reading…
“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.’ “