CHICAGO — Treatment with binimetinib improved PFS, disease control rate and overall response rate compared with dacarbazine among patients with NRAS–mutant melanoma, according to results of the open-label phase 3 NEMO study presented at the ASCO Annual Meeting.
“NRAS mutations are present in approximately 20% of all patients with metastatic melanoma,” Reinhard Dummer, MD, professor of dermatology at University Hospital Zurich, said during his presentation. “Preclinical studies have shown that NRAS–mutated melanomas are sensitive to MEK inhibitors. There are data that suggest that NRAS–mutated melanoma has a more aggressive disease outcome and more brain metastases, and there is really an unmet medical need in this patient population, especially after failure of immunotherapy.”
Dummer and colleagues compared binimetinib (MEK162, Array BioPharma) with dacarbazine in patients with unresectable or metastatic NRAS–mutated melanoma.
The researchers randomly assigned patients to twice-daily oral binimetinib (45 mg; n = 269) or IV dacarbazine (1,000 mg/m2) every 3 weeks (n = 133). The study included previously untreated patients, as well as patients who progressed after treatment with immunotherapy.
PFS served as the primary endpoint, with OS defined as a key secondary endpoint. Other secondary endpoints included ORR and disease control rate.
In the overall cohort, patients assigned binimetinib achieved a median PFS of 2.8 months (range, 2.8-3.6), compared with 1.5 months (95% CI, 1.5-1.7) for patients assigned dacarbazine (HR = 0.62; 95% CI, 0.47-0.8).
Among 85 patients previously treated with immunotherapy, those who received binimetinib achieved a median PFS of 5.5 months (95% CI, range, 2.8-7.6), compared with 1.6 months (95% CI, 1.5-2.8) for patients treated with dacarbazine (HR = 0.46; 95% CI, 0.26-0.81).
Binimetinib induced longer PFS in patients without prior treatment (2.8 months vs. 1.5 months; HR = 0.7; 95% CI, 0.53-0.94), and those with high lactate dehydrogenase levels (2.1 months vs. 1.4 months; HR = 0.45; 95% CI, 0.28-0.71).
Patients assigned binimetinib also had a higher confirmed ORR (15% vs. 7%; P = .0015) and disease control rate (58% vs. 25%; P < .001).
The median duration of response for binimetinib was 6.9 months.
Dummer reported a median OS of 11 months (95% CI, 8.9-13.6) for binimetinib and 10.1 months (95% CI, 7-16.5) for dacarbazine. However, he cautioned that these data were still raw and that follow-up for OS outcomes remained ongoing.
Grade 3 or worse adverse events included increased creatine phosphokinase (binimetinib, 19% vs. dacarbazine, 0%), rash (4% vs. 0%), dermatitis acneiform (3% vs. 0%), fatigue (2% vs. 3%) and asthenia (3% vs. 4%).
“NEMO is the largest study to date performed in patients with NRAS–mutated melanoma, and it was a logistic challenge to get all of these patients included,” Dummer said. “Based on these data, I think that binimetinib can be considered a new treatment option for patients who have failed immunotherapy.” – by Cameron Kelsall
Dummer R, et al. Abstract 9500. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
Dummer reports research funding and honoraria from, as well as consultant roles with, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Novartis and Roche. Please see the abstract for a list of all other researchers’ relevant financial disclosures.