“A pioneering drug developed to treat women with inherited cancers can also benefit men with advanced prostate cancer, a major new clinical trial concludes.
“The trial is a milestone in cancer treatment as the first to show the benefits of ‘precision medicine’ in prostate cancer – with treatment matched to the particular genetic characteristics of a man’s tumour.
“Olaparib, the world’s first drug to reach the market targeted against inherited cancer mutations, was found to benefit as many as a third of patients with prostate cancer, including many who did not inherit cancer genes but whose tumours had acquired defects in DNA repair.”
“In 2008 Linardou et al published results of a meta-analysis of studies in advanced non–small cell lung cancer (NSCLC) and metastatic colorectal cancer. They extracted data on 1008 patients; 165 from 17 manuscripts for the NSCLC portion of the meta-analysis had KRAS mutations. They sought to establish whether or not KRAS mutations could be candidate predictive biomarkers for antiepidermal growth factor (EGFR) treatments. The analysis yielded empirical evidence that KRAS mutations are highly specific negative predictors of response to EGFR tyrosine kinase inhibitors (TKIs) when given as single agents to patients with advanced NSCLC. Further implicating an association of KRAS mutations with poor outcomes, a retrospective analysis of data from 1036 patients with stage IV lung adenocarcinoma and KRAS mutation evaluated between 2002 and 2009, found the presence of KRAS mutations to be associated with shorter survival (HR, 1.21; P = .48).”
“Exelixis, Inc.EXEL, -1.02% today announced positive overall survival (OS) results from coBRIM, the phase 3 pivotal trial evaluating cobimetinib, a specific MEK inhibitor discovered by Exelixis, in combination with vemurafenib in previously untreated patients with unresectable locally advanced or metastatic melanoma carrying a BRAF V600 mutation. Exelixis’ collaborator Genentech, a member of the Roche Group, informed the company that coBRIM met its secondary endpoint of demonstrating a statistically significant and clinically meaningful increase in overall survival for patients receiving the combination of cobimetinib and vemurafenib, as compared to vemurafenib monotherapy. Ongoing study monitoring did not identify any new safety signals. Long-term safety data are expected later this year. These data will be the subject of a presentation at an upcoming medical meeting.”
“Small cell lung cancer (SCLC) is an aggressive disease that is difficult to treat and is frequently only diagnosed when it has spread to other parts of the body (metastasised). Five-year survival rates in SCLC, which accounts for about 14% of all lung cancers, are very low, at only six percent. But today US researchers will present two novel findings with important implications for treatment at the 2015 European Cancer Congress.
“Dr M. Catherine Pietanza, MD, an Assistant Attending Physician at the Memorial Sloan Kettering Cancer Center, New York, USA, will report on results from a phase I trial of a novel agent, rovalpituzumab tesirine (Rova-T, or S16LD6.5), in 79 patients with SCLC who had progressed after first line (given when the disease is newly diagnosed) or second line therapy (given when the disease progresses or recurs).
” ‘While other cancers have multiple treatment options, there is only one agent approved in SCLC, and none available in the third line setting; the outlook for these patients is dismal,’ she will say. Third line therapy is given after first and second line treatments have failed to halt the progression of disease.”
“ ‘The primary underpinning of the trial comes from genetic characterization of various cancer types, which has become increasingly common place but is not yet routine,’ Keith T. Flaherty, MD, an oncologist at Massachusetts General Hospital, associate professor at Harvard Medical School andECOG-ACRIN chair of the NCI-MATCH trial, told HemOnc Today. ‘When looking at cancers as defined by their site of origin, there are threads of continuity across those cancer types. Within a cancer type, there also is heterogeneity, and understanding what this patchwork looks like was really the main motivator for setting up a trial like this.’ “
“Targeted treatments for cancer have been extending and saving lives for more than 15 years—precision medicine isn’t a new idea in oncology. Now drugs pioneered on select, specific cancers are, one by one, finding new applications.
“The first wave of targeted drug approvals were for cancers associated with specific mutations. Herceptin (traztuzumab) led the way, approved in 1998. It’s a monoclonal antibody deployed against the HER2/neu receptor that is overabundant in some aggressive and early-onset breast cancers. Robert Bazell’s excellent book Her 2 tells the tale.
“In 2001 came the blockbuster Gleevec (imatinib), a small molecule tyrosine kinase inhibitor that intercepts signals to divide. Erin Zammett’s My So-Called Normal Life with Cancer relates that story. A very young editor at Glamour magazine when a routine check-up revealed chronic myelogenous leukemia, Erin’s recovery was one of the first of thousands thanks to this now famous drug.”
“She had come to see me as a second opinion; diagnosed with uterine serous cancer, one of the more aggressive types of uterine cancers. At surgery they found that it had metastasized to her nodes—stage III disease. The surgery was successful, though, and she had been treated with adjuvant chemotherapy with the hope it was curative. Two years later, she developed abdominal pain. A work-up showed that her CA-125 was elevated, which prompted a scan, and a diagnosis of hepatic metastases. Her doctors recommended repeat treatment with chemotherapy—carboplatin and paclitaxel. ‘It didn’t work the first time, so I am not sure doing it all over again makes sense.’ “
“A new kind of cancer study supports the idea that traditional treatment can be turned on its head, with patients given targeted therapy based not on where their tumors started but on their own genetic mutations.
“Researchers used a targeted melanoma drug to treat patients with a range of cancers, from lung cancer to brain cancer, who weren’t being helped by traditional chemotherapy any more. Even though they had many different types of tumors, they all had one thing in common — a genetic mutation called BRAFV600.
“It’s a mutation familiar to doctors who treat melanoma, the deadliest form of skin cancer. It’s seen in about half of melanoma cases. A pill called vemurafenib, sold under the brand name Zelboraf, specifically targets the mutation. It helps about half of patients with melanoma who have the mutation.
“The same mutation is sometimes seen in colon cancer, lung cancer, thyroid cancer, brain tumors and some blood cancers.”
“While targeting HER2 mutations is mainly associated with breast cancer, there could be therapeutic potential with anti-HER2 agents in non-small cell lung cancer (NSCLC). At this year’s International Lung Cancer Congress, Corey Langer, MD, discussed the potential for afatinib and neratinib—dual inhibitors of EGFR and HER2—in NSCLC, as well as the need for additional research, in order to truly comprehend HER2 targeted therapy in this particular setting.
“HER2 mutations occur in about 2% to 4% of patients with NSCLC, and for the most part, they are mutually exclusive with other molecular drivers (eg, EGFR, KRAS), according to Langer, director of Thoracic Oncology at the Abramson Cancer Center of the University of Pennsylvania. “Similar to EGFR and ALK, the HER2 mutations are more common in women, never-smokers, and adenocarcinoma histology,” Langer added.
“Regarding use of afatinib in these patients, Langer said, ‘There are limited but encouraging data in patients with HER2-mutant NSCLC treated with either afatinib or afatinib plus paclitaxel.’ “