TY - JOUR
T1 - Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial
AU - Dummer, R.
AU - Schadendorf, D.
AU - Ascierto, P.A.
AU - Arance, A.
AU - Dutriaux, C.
AU - Di Giacomo, A.M.
AU - Rutkowski, P.
AU - Del Vecchio, M.
AU - Gutzmer, R.
AU - Mandala, M.
AU - Thomas, L.
AU - Demidov, L.
AU - Garbe, C.
AU - Hogg, D.
AU - Liszkay, G.
AU - Queirolo, P.
AU - Wasserman, E.
AU - Ford, J.
AU - Weill, M.
AU - Sirulnik, L.A.
AU - Jehl, V.
AU - Bozón, V.
AU - Long, G.V.
AU - Flaherty, K.
N1 - Cited By :4
Export Date: 14 July 2017
CODEN: LOANB
Correspondence Address: Dummer, R.; Department of Dermatology, University Hospital Zürich Skin Cancer CenterSwitzerland; email: reinhard.dummer@usz.ch
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S66
PY - 2017
Y1 - 2017
N2 - Background There are no established therapies specific for NRAS-mutant melanoma despite the emergence of immunotherapy. We aimed to assess the efficacy and safety of the MEK inhibitor binimetinib versus that of dacarbazine in patients with advanced NRAS-mutant melanoma. Methods NEMO is an ongoing, randomised, open-label phase 3 study done at 118 hospitals in 26 countries. Patients with advanced, unresectable, American Joint Committee on Cancer stage IIIC or stage IV NRAS-mutant melanoma who were previously untreated or had progressed on or after previous immunotherapy were randomised (2:1) to receive either binimetinib 45 mg orally twice daily or dacarbazine 1000 mg/m2 intravenously every 3 weeks. Randomisation was stratified by stage, performance status, and previous immunotherapy. The primary endpoint was progression-free survival assessed by blinded central review in the intention-to-treat population. Safety analyses were done in the safety population, consisting of all patients who received at least one study drug dose and one post-baseline safety assessment. This study is registered with ClinicalTrials.gov, number NCT01763164 and with EudraCT, number 2012-003593-51. Findings Between Aug 19, 2013, and April 28, 2015, 402 patients were enrolled and randomly assigned, 269 to binimetinib and 133 to dacarbazine. Median follow-up was 1·7 months (IQR 1·4–4·1). Median progression-free survival was 2·8 months (95% CI 2·8–3·6) in the binimetinib group and 1·5 months (1·5–1·7) in the dacarbazine group (hazard ratio 0·62 [95% CI 0·47–0·80]; one-sided p<0·001). Grade 3–4 adverse events seen in at least 5% of patients the safety population in either group were increased creatine phosphokinase (52 [19%] of 269 patients in the binimetinib group vs none of 114 in the dacarbazine group), hypertension (20 [7%] vs two [2%]), anaemia (five [2%] vs six [5%]), and neutropenia (two [1%] vs ten [9%]). Serious adverse events (all grades) occurred in 91 (34%) patients in the binimetinib group and 25 (22%) patients in the dacarbazine group. Interpretation Binimetinib improved progression-free survival compared with dacarbazine and was tolerable. Binimetinib might represent a new treatment option for patients with NRAS-mutant melanoma after failure of immunotherapy. Funding Array BioPharma and Novartis Pharmaceuticals Corporation. © 2017 Elsevier Ltd
AB - Background There are no established therapies specific for NRAS-mutant melanoma despite the emergence of immunotherapy. We aimed to assess the efficacy and safety of the MEK inhibitor binimetinib versus that of dacarbazine in patients with advanced NRAS-mutant melanoma. Methods NEMO is an ongoing, randomised, open-label phase 3 study done at 118 hospitals in 26 countries. Patients with advanced, unresectable, American Joint Committee on Cancer stage IIIC or stage IV NRAS-mutant melanoma who were previously untreated or had progressed on or after previous immunotherapy were randomised (2:1) to receive either binimetinib 45 mg orally twice daily or dacarbazine 1000 mg/m2 intravenously every 3 weeks. Randomisation was stratified by stage, performance status, and previous immunotherapy. The primary endpoint was progression-free survival assessed by blinded central review in the intention-to-treat population. Safety analyses were done in the safety population, consisting of all patients who received at least one study drug dose and one post-baseline safety assessment. This study is registered with ClinicalTrials.gov, number NCT01763164 and with EudraCT, number 2012-003593-51. Findings Between Aug 19, 2013, and April 28, 2015, 402 patients were enrolled and randomly assigned, 269 to binimetinib and 133 to dacarbazine. Median follow-up was 1·7 months (IQR 1·4–4·1). Median progression-free survival was 2·8 months (95% CI 2·8–3·6) in the binimetinib group and 1·5 months (1·5–1·7) in the dacarbazine group (hazard ratio 0·62 [95% CI 0·47–0·80]; one-sided p<0·001). Grade 3–4 adverse events seen in at least 5% of patients the safety population in either group were increased creatine phosphokinase (52 [19%] of 269 patients in the binimetinib group vs none of 114 in the dacarbazine group), hypertension (20 [7%] vs two [2%]), anaemia (five [2%] vs six [5%]), and neutropenia (two [1%] vs ten [9%]). Serious adverse events (all grades) occurred in 91 (34%) patients in the binimetinib group and 25 (22%) patients in the dacarbazine group. Interpretation Binimetinib improved progression-free survival compared with dacarbazine and was tolerable. Binimetinib might represent a new treatment option for patients with NRAS-mutant melanoma after failure of immunotherapy. Funding Array BioPharma and Novartis Pharmaceuticals Corporation. © 2017 Elsevier Ltd
U2 - 10.1016/S1470-2045(17)30180-8
DO - 10.1016/S1470-2045(17)30180-8
M3 - Article
VL - 18
SP - 435
EP - 445
JO - The Lancet Oncology
JF - The Lancet Oncology
SN - 1470-2045
IS - 4
ER -