CHICAGO — Binimetinib may represent a new effective therapy for patients with NRAS-mutant melanoma, both before and after immunotherapy. That is the conclusion of the phase 3 NEMO study, results of which were presented at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting.1
Patients treated with binimetinib, an oral, selective, ATP-uncompetitive inhibitor of MEK1 and MEK2, showed improvements over dacarbazine in several clinically relevant end points, including progression-free survival, overall response rate, and disease control rate and was well-tolerated, said Reinhard Dummer, MD, University Hospital Zurich, Zurich, Switzerland.
The NRAS mutation occurs in approximately 20% of patients with metastatic melanoma; however, no therapies currently exist to treat this specific mutation. Despite emergence of immunotherapies as effective treatments in melanoma, there is a “substantial unmet clinical need, particularly after failure of immunotherapy, he said.
The open-label phase 3 study randomly assigned 402 patients with advanced unresectable/metastatic cutaneous NRAS-mutant melanoma previously untreated or had progressed on/after prior immunotherapy 2:1 to binimetinib 45 mg orally twice daily (n = 269) or dacarbazine 1000 mg/m2 intravenously (n = 133) every 3 weeks.
Progression-free survival was 2.8 months (95% CI, 2.8-3.6) in the binimetinib arm and 1.5 months (95% CI, 1.5-1.7) in the dacarbazine arm (HR, 0.62; 95% CI, 0.47-0.80; P < .001), which was longer in patients with prior immunotherapy (5.5 months) and normal LDH (3.9 months).
Confirmed overall response and disease control rates for binimetinib were 15% (95% CI, 11%-20%) and 58% (95% CI, 52%-64%) for binimetinib vs 7% (95% CI, 3%-13%) and 25% (95% CI, 18%-33%) for dacarbazine (P = .015 [ORR]; P < .001 [DCR]), respectively. Median duration of response on binimetinib was 6.9 months.
Dr. Dummer presented early median overall survival results; which were 11.0 months in the binimetinib arm and 10.1 months in the dacarbazine arm (HR, 1.00; 95% CI, 0.75-1.33; P = .499). Nearly half of patients in both arms used immunotherapy after treatment discontinuation, which included ipilimumab, nivolumab, and pembrolizumab.
Grade 3/4 adverse events reported in 5% or greater of patients in either group were increased CPK (19% binimetinib, 0% dacarbazine), hypertension (7% binimetinib, 2% dacarbazine), anemia (2% binimetinib, 5% dacarbazine) and neutropenia (1% binimetinib, 9% dacarbazine), Dr. Dummer said.
1. Dummer R, Schadendorf D, Ascierto PA, et al. Results of NEMO: A phase III trial of binimetinib (BINI) vs dacarbazine (DTIC) in NRAS-mutant cutaneous melanoma. Oral presentation at: ASCO 2016 Annual Meeting; June 3-7, 2016; Chicago, IL.