“In patients with advanced BRAF V600–mutant melanoma, combining the BRAF inhibitor encorafenib (Braftovi) with the MEK inhibitor binimetinib (Mektovi) improved overall survival compared to vemurafenib (Zelboraf) or encorafenib as monotherapy, with a favorable toxicity profile, according to updated results from the phase III COLUMBUS trial.
“Combined BRAF/MEK inhibitor therapy is standard of care in advanced BRAF V600–mutant melanoma, but approved combinations have unique toxicities that may impact the ability to deliver optimal treatment (ie, vemurafenib/cobimetinib [Cotellic] is associated with photosensitivity).”
“In the international phase III BRIM8 trial reported in The Lancet Oncology, Maio et al found inconclusive evidence of benefit of adjuvant vemurafenib treatment in patients with BRAF V600–mutant melanoma.”
“Vemurafenib offered numerical improvement in disease-free survival in a study of patients with completely resected stage IIC to IIIC BRAF V600 mutation–positive melanoma, but the results did not reach statistical significance. The benefit was bigger in those with stage IIC to IIIB disease, but this should be considered exploratory at this point.
” ‘Despite full resection, patients with stage IIC to III melanoma remain at high risk for disease recurrence and death,’ wrote study authors led by Michele Maio, MD, of University Hospital of Siena in Italy. ‘This situation warrants the use of adjuvant approaches to improve clinical outcomes.’ ”
“Triplet therapy for advanced, BRAF V600-mutant melanoma led to objective responses in 73% of a small group of patients enrolled in a phase I trial, according to updated results reported at the 2017 ESMO Annual Congress in Madrid.
“Ongoing follow-up in the trial showed that 11 of 15 patients responded to the combination of pembrolizumab (Keytruda), dabrafenib (Tafinlar), and trametinib (Mekinist). Seven of the 11 responding patients had not progressed after a median follow-up of 20 months. ‘Updated results of the phase I portion of the KEYNOTE-022 trial confirmed previously reported efficacy of this triplet combination,’ said Antoni Ribas, MD, PhD, a professor of medicine, surgery, and molecular and medical pharmacology at the University of California at Los Angeles. ‘The results demonstrated durability of responses. No late or unexpected toxicities occurred with longer follow-up. The randomized phase II portion of KEYNOTE-022 is ongoing.’ ”
“More than one-fourth of patients with advanced BRAF V600-mutant melanoma remained alive at 5 years after treatment with the combination of dabrafenib (Tafinlar) and trametinib (Mekinist), long-term follow-up from a randomized trial showed.
“In the subgroup of patients with normal baseline lactate dehydrogenase (LDH) and fewer than 3 organ sites with metastases, half remained at alive at 5 years. No new safety signals emerged during long-term follow-up, as reported at the 2017 ASCO Annual Meeting in Chicago.”
“Combination treatment with cobimetinib and vemurafenib resulted in significantly improved overall and progression-free survival in patients with previously untreated BRAF V600–mutated advanced melanoma, according to updated efficacy results of the coBRIM trial published in Lancet Oncology.
“ ‘Patients treated with the combination of cobimetinib and vemurafenib achieved a higher objective response, longer progression-free survival, and longer overall survival compared with patients treated with vemurafenib alone,’ wrote researchers led by Paolo A. Ascierto, MD, of the Istituto Nazionale Tumori Fondazione G Pascale in Naples, Italy. ‘The combination of cobimetinib and vemurafenib was recently approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of advanced BRAF V600–mutant melanoma and represents a new standard of treatment for patients with this disease.’ ”
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“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.’ “
“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.”
“The combination of nivolumab and ipilimumab has received accelerated FDA approval as a treatment for patients with BRAF V600 wild-type (WT) unresectable or metastatic melanoma, based on findings from the phase II CheckMate-069 study.
” ‘Historically, metastatic melanoma has been a difficult disease to treat. Now, a new treatment option based on the combination of two valued immuno-oncology agents demonstrates significant efficacy versus ipilimumab in metastatic melanoma,’ said Jedd D. Wolchok, MD, PhD, chief, Melanoma and Immunotherapeutics Service, Department of Medicine and Ludwig Center at Memorial Sloan Kettering Cancer Center, in a statement. ‘Today’s approval represents a step forward for the melanoma community, providing hope for patients with metastatic melanoma.’ ”