Personalizing Cancer Therapies May Combat Resistance to Targeted Therapy Drugs

“The use of drugs that target genetic mutations driving the growth of tumors has revolutionized treatment for several serious forms of cancer, but in almost every case, tumors become resistant to the drugs’ therapeutic effects and resume growth, often through the emergence of new mutations, which has spurred the development of more powerful drugs that can overcome resistance mutations. In the Dec. 24 issue of New England Journal of Medicine, Massachusetts General Hospital (MGH) physicians report their study examining the evolution of drug resistance in a lung cancer patient treated with multiple different targeted therapies. When resistance developed to the third targeted therapy, the new mutation actually restored the cancer’s response to the very first targeted therapy drug used to treat the patient.”

FDA Grants Genentech’s Alecensa® (Alectinib) Accelerated Approval for People with a Specific Type of Lung Cancer

“Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) granted accelerated approval to Alecensa® (alectinib) for the treatment of people with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. In the pivotal studies, Alecensa shrank tumors in up to 44 percent of people with ALK-positive NSCLC who progressed on crizotinib (objective response rate [ORR] of 38 percent [95 percent CI 28-49] and 44 percent [95 percent CI 36-53]). In a subset of people with tumors that spread to the brain or other parts of the central nervous system (CNS), Alecensa shrank CNS tumors in about 60 percent of people (CNS ORR of 61 percent [95 percent CI 46-74]).”

Missense HER2 Mutations May Not Respond to Targeted Therapies

“Not all HER2 genes are capable of causing cancer growth or spread, and thus may also fail to predict response to anticancer drugs that target the gene, according to a recent study published in the Proceedings of the National Academy of Sciences.

“Roughly 5% of breast cancers contain HER2 missense mutations, which primarily occur in the absence of HER2 gene amplification. Unlike most HER2 genes, missense mutations do not cause an overproduction of proteins and, as a result, classify as negative for HER2 by FISH or immunohistochemistry assays.

“To determine if these HER2 missense mutations could be targets for HER2-directed therapies that are currently approved for the treatment of HER2 gene-amplified breast cancers, researchers from Johns Hopkins Sidney Kimmel Comprehensive Cancer Center individually placed 7 missense mutations found in human breast cancers into normal and cancerous human breast cells that do not produce excessive amounts of the HER2 protein or have any baseline HER2 mutations.”

Targeted Therapy Combinations Still Key in Metastatic Melanoma

“Combinations of targeted therapies continue to advance toward full regulatory approval for patients with metastatic or unresected melanoma, given the substantial benefits seen with these agents. At this time, the FDA is considering two applications for separate combinations of BRAF and MEK inhibiting agents for patients with unresectable or metastatic BRAFV600 mutation-positive melanoma.

“ ‘The future of the treatment of melanoma is clearly going to be in combinations, both for targeted therapy and for immunotherapy,’ said Jeffrey S. Weber, MD, PhD, who recently joined the NYU Langone Medical Center. ‘Already, there is an FDA-approved combination therapy that is targeted; that is dabrafenib and trametinib. There are new combinations coming up, mainly concerning CDK 4/6 and MEK inhibitors in NRAS-mutated but BRAF wild-type melanoma, which is an unmet medical need.’ “

Super Patient: Janet Freeman-Daily Joins a Clinical Trial—and Beats the Odds on Lung Cancer

In March 2011, Janet Freeman-Daily was about to take a long family trip to China. She’d been coughing for a while, so she asked her doctor for an antibiotic as a precaution before leaving. Even so, she came back in May with a respiratory infection that wouldn’t go away.

Her doctor ordered an X-ray and then a CT scan. “Before I got home, they called and said they’d like to do a bronchoscopy,” Janet says. The scan revealed a 7-cm mass in her left lung, and biopsies showed it was non-small cell lung cancer (NSCLC) and that it had spread to several lymph nodes. Continue reading…

Landmark Clinical Trial Shows Gene-Targeted Drug Can Treat Prostate Cancer

“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.”

JUNIPER Trial Branches Out in KRAS Mutation-Positive Advanced NSCLC

“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 Announces Positive Overall Survival Results from Phase 3 Pivotal Trial of Cobimetinib in Combination with Vemurafenib in Patients with BRAF V600 Mutation-Positive Advanced Melanoma

“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.”

First 'Targeted' Treatment for Small Cell Lung Cancer Shows Promise

“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.”