Adjuvant therapy with BRAF/MEK inhibitors should be preferred for patients with BRAF-mutant non-ulcerated stage III melanoma.

Noting that the combination of dabrafenib and trametinib has been approved in Europe and the USA for individuals with BRAF V600E mutation-positive NSCLC, the researchers say “combination therapy consisting of a BRAF inhibitor and an MEK inhibitor has now become standard of care” for these patients.

Data from the phase Ib TATTON trial suggest that patients with EGFR -mutated non-small-cell lung cancer who have progressed on prior EGFR–tyrosine kinase inhibitor therapy could benefit from adding either the MET inhibitor savolitinib or the MEK inhibitor selumetinib to osimertinib.

Roy Herbst provides his views on the phase Ib TATTON study that combined osimertinib with either the MET inhibitor savolitinib or the MEK inhibitor selumetinib in the advanced, resistant NSCLC setting (2:53).

An updated analysis of the phase III COLUMBUS trial adds to the evidence supporting a combination of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib in patients with advanced BRAF V600-mutant melanoma.

The combination of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib has favorable efficacy and tolerability relative to either encorafenib or vemurafenib alone in patients with advanced melanoma harboring BRAF mutations, phase III trial findings indicate. Read the accompanying comment by Eva Muñoz Couselo

An updated analysis of the phase III COLUMBUS trial adds to the evidence supporting a combination of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib in patients with advanced BRAF V600-mutant melanoma.

This edition of the medwireNews podcast focuses on a recent trial of the MEK inhibitor selumetinib in metastatic uveal melanoma. Advisory Board member and study author Paul Nathan outlines the findings and discusses the wider implications.

Receiving neoadjuvant plus adjuvant dabrafenib and trametinib significantly improves event-free survival compared with standard care in patients with high-risk melanoma, phase II study findings indicate.

Adjuvant combination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib halves the risk for relapse in patients with stage III melanoma with BRAF V600E or V600K mutations, show results from the COMBI-AD trial.

In an accompanying comment , Rafael Rosell (Germans Trias i Pujol Health Sciences Institute and Hospital, Barcelona, Spain) and Niki Karachaliou (University Hospital Sagrat Cor, Barcelona, Spain) conclude that Johnson et al’s findings, combined with those from the previous two cohorts “clearly indicate that the combination of a BRAF inhibitor plus a MEK inhibitor induces significant response and benefit in progression-free survival in patients with BRAF V600E -mutant NSCLC and paves the way to further validate the combination in the frequent additional group of NSCLCs with BRAF -inactivating mutations.”

Binimetinib could be incorporated into the treatment pathway of patients with advanced melanoma harboring NRAS mutations, say researchers who found a progression-free survival benefit with the MEK inhibitor over dacarbazine.

Jerchel et al. report on their application of next-generation sequencing of 13 RAS pathway genes with a risk-stratified survival analysis in a cohort of pediatric B-cell precursor acute lymphoblastic leukemia patients. Leukemia  DOI: 10.1038/leu.2017.303

When stratified by receipt of prior BRAF or MEK inhibitor therapy, intracranial response rates were a respective 50% and 21% for patients who were naïve to such treatment in the combination and nivolumab alone arms, falling to 16% in either arm for those who had received BRAF or MEK inhibitors previously.

They add: “Although selumetinib demonstrated little suggestion of benefit in SELECT-1, it may be premature to conclude that other [MEK inhibitors] will be ineffective given differences in their inhibitory mechanism.”

. --- Researcher Georgina Long (University of Sydney, New South Wales, Australia) and co-authors have found that patients with BRAF V600E/K-mutant metastatic melanoma derive durable clinical benefits from the addition of the MEK inhibitor trametinib to dabrafenib, a BRAF inhibitor.

medwireNews : The US FDA has granted general approval  for combined BRAF and MEK inhibitor therapy for patients with metastatic non-small-cell lung cancer (NSCLC) shown to have a BRAF V600E mutation.