Drugs That Work in Melanomas with BRAF Mutation Also Work in Lung Cancers with Same Mutation

“A subset of lung cancer patients can derive important clinical benefits from drugs that are more commonly used to treat melanoma, the authors of a new academic clinical trial in Europe have reported at the European Lung Cancer Conference (ELCC) in Geneva, Switzerland.

“Dr. Oliver Gautschi, a medical oncologist from Lucern Cantonal Hospital in Switzerland, presented the results of the retrospective EURAF cohort study, which included lung cancer patients whose tumours carried specific mutations in the BRAF gene. The study was conducted by a network of European oncologists, without company involvement.

“BRAF mutations are commonly seen in melanoma patients, and are found in about 2% of lung adenocarcinomas, Gautschi explains. Several inhibitors of the B-Raf protein, including vemurafenib and dabrafenib, have been developed for use in melanoma patients, however there is currently no approved drug for BRAF-mutant lung cancer.

“As a result, experience with B-Raf inhibitors in lung cancer remains limited. ‘In the current study, we wanted to find out how many patients in Europe received B-Raf inhibitors outside of a clinical trial, and what their outcomes were,’ Gautschi says.

“The EURAF study gathered information on 35 lung cancer patients who had been identified as carrying BRAF mutations, who were treated with B-Raf inhibitors between 2012 and 2014.”


Phase II Trial Shows Overall Survival Benefit With VT-122 Plus Sorafenib in Advanced Hepatocellular Carcinoma

The gist: People with advanced hepatocellular carcinoma may benefit from treatment with a combination of the drugs VT-122 and sorafenib (Nexavar). That was the conclusion of a recent clinical trial—a research study with volunteer patients. The goal of the trial was to test the combination treatment. In the trial, people who took the combination had an 11-month increase in overall survival compared to people who took only sorafenib.

“The investigational agent VT-122 appeared to benefit survival when combined with sorafenib (Nexavar) in patients with advanced hepatocellular carcinoma, according to data presented at the 8th Annual International Liver Cancer Association Conference in Kyoto, Japan. Researchers reported an 11-month increase in median overall survival in patients treated with VT-122 plus sorafenib, compared to those receiving sorafenib alone.

“VT-122 is a novel, oral, chronodosed combination of the nonsteroidal anti-inflammatory drug (NSAID) etodolac and the beta-blocker propranolol. The investigational compound inhibits prostaglandin and beta-adrenergic signaling to reduce tumor-promoting inflammation and restore a tumor-suppressing immune state…

“In this phase II randomized, open-label, controlled clinical trial, 24 patients with advanced hepatocellular carcinoma were randomly assigned to receive VT-122 plus sorafenib or sorafenib alone.”


Drugs to Avoid in Patients on Tyrosine Kinase Inhibitors

Editor’s note: More and more people with cancer are being treated with drugs known as tyrosine kinase inhibitors (TKIs). As with any other drug, oncologists who prescribe TKIs must be aware of other drugs a patient is taking to ensure there will not be a dangerous drug-drug interaction. Researchers recently published a report outlining known and potential drug-drug interactions between TKIs and other drugs. Oncologists and patients may wish to take these into account when considering cancer treatment with TKIs.

“With the rapid and widespread uptake of tyrosine kinase inhibitors (TKIs) in oncology over the past several years, serious drug–drug interactions are an “increasing risk,” according a new report.

“To guarantee the safe use of TKIs, ‘a drugs review for each patient is needed,’ write Frank G.A. Jansman, PharmD, PhD, from Deventer Hospital in the Netherlands, and colleagues in a review published in the July issue of the Lancet Oncology.

“The review provides a comprehensive overview of known and suspected interactions between TKIs and conventional prescribed drugs, over-the-counter drugs, and herbal medicines.

“All 15 TKIs approved to date by the US Food and Drug Administration or the European Medicines Agency are evaluated.

“They are axitinib (Inlyta, Pfizer), crizotinib (Xalkori, Pfizer), dasatinib (Sprycel, Bristol-Myers Squibb and Otsuka America), erlotinib (Tarceva, Osi Pharmaceuticals), gefitinib (Iressa, AstraZeneca), imatinib (Gleevec, Novartis), lapatinib (Tykerb, GlaxoSmithKline), nilotinib (Tasigna, Novartis), pazopanib (Votrient, GlaxoSmithKline), regorafenib (Stivarga, Bayer), ruxolitinib (Jakafi, Incyte), sorafenib (Nexavar, Bayer), sunitinib (Sutent, Pfizer), vandetanib (Caprelsa, AstraZeneca), and vemurafenib (Zelboraf, Roche).”


RET Mutations May Emerge as New Target for Lung Cancer Treatments

A certain type of mutation in a protein, called RET, occurs in a significant subset of lung cancer patients, a recent study shows. Known as ‘rearrangements,’ these mutations fuse the RET gene with other nearby genes, resulting in a RET protein that contains parts of other proteins and is hyperactive. Patients with similar rearrangement mutations in another gene, ALK, can experience drastic improvements from treatment with ALK inhibitors such as crizotinib (Xalkori). This raises the hope that patients with RET rearrangement mutations may be similarly helped by drugs that block RET–either novel RET inhibitors or existing tyrosine kinase inhibitors (TKIs), such as vandetanib (Caprelsa), sunitinib (Sutent), sorafenib (Nexavar), or ponatinib (Iclusig). Identifying patients who may benefit from such treatments would be made easier by the new test for RET mutations developed by the study’s authors. When examining a group of patients with lung adenocarcinoma, a type of non-small cell lung cancer (NSCLC), who did not have mutations in other cancer-relevant genes, the researchers found that 15% had RET rearrangement mutations.


Tarceva May Be More Effective in Advanced NSCLC When Combined with Other Targeted Therapies

An analysis of multiple clinical trials compared erlotinib (Tarceva) alone to combining Tarceva with other targeted therapies as second-line treatment for advanced non-small cell lung cancer (NSCLC). In the various trials, Tarceva was combined with bevacizumab (Avastin), bortezomib (Velcade), everolismus (Afinitor), sorafenib (Nexavar), sunitinib (Sutent), entinostat, tivantinib, and R1507. While combined therapy produced more side effects, it was more effective than Tarceva alone. Notably, the trials included many patients who had not been tested for mutations in the EGFR and KRAS genes. In patients who had EGFR mutations and/or lacked KRAS mutations, Tarceva alone tended to control cancer progression better than combined therapy, highlighting the importance of biomarker testing to identify which patients are most likely to benefit from different therapies.