Nivolumab was associated with significant improvements in overall survival and progression-free survival, as compared with dacarbazine, among previously untreated patients who had metastatic melanoma without a BRAF mutation. (Funded by Bristol-Myers Squibb; CheckMate 066 ClinicalTrials.gov number, NCT01721772.).

IMPORTANCEThis analysis provides long-term follow-up in patients with BRAF wild-type advanced melanoma receiving first-line therapy based on anti-programmed cell death 1 receptor inhibitors.OBJECTIVE To compare the 3-year survival with nivolumab vs that with dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma. DESIGN, SETTING, AND PARTICIPANTSThis follow-up of a randomized phase 3 trial analyzed 3-year overall survival data from the randomized, controlled, double-blind CheckMate 066 phase 3 clinical trial. For this ongoing, multicenter academic institution trial, patients were enrolled from January 2013 through February 2014. Eligible patients were 18 years or older with confirmed unresectable previously untreated stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 but without a BRAF mutation.INTERVENTIONS Patients were treated until progression or unacceptable toxic events with nivolumab (3 mg/kg every 2 weeks plus dacarbazine-matched placebo every 3 weeks) or dacarbazine (1000 mg/m 2 every 3 weeks plus nivolumab-matched placebo every 2 weeks). MAIN OUTCOME AND MEASURE Overall survival.RESULTS At minimum follow-ups of 38.4 months among 210 participants in the nivolumab group (median age, 64 years [range, 18-86 years]; 57.6% male) and 38.5 months among 208 participants in the dacarbazine group (median age, 66 years [range, 25-87 years]; 60.1% male), 3-year overall survival rates were 51.2% (95% CI, 44.1%-57.9%) and 21.6% (95% CI, 16.1%-27.6%), respectively. The median overall survival was 37.5 months (95% CI, 25.5 months-not reached) in the nivolumab group and 11.2 months (95% CI, 9.6-13.0 months) in the dacarbazine group (hazard ratio, 0.46; 95% CI, 0.36-0.59; P < .001). Complete and partial responses, respectively, were reported for 19.0% (40 of 210) and 23.8% (50 of 210) of patients in the nivolumab group compared with 1.4% (3 of 208) and 13.0% (27 of 208) of patients in the dacarbazine group. Additional analyses were performed on outcomes with subsequent therapies. Treatment-related grade 3/4 adverse events occurred in 15.0% (31 of 206) of nivolumab-treated patients and in 17.6% (36 of 205) of dacarbazine-treated patients. There were no deaths due to study drug toxic effects.CONCLUSIONS AND RELEVANCE Nivolumab led to improved 3-year overall survival vs dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma.

Supplemental digital content 2.pdf-Summary of the characteristics of all included studies on treatment for metastatic uveal melanoma Intervention Study Publication year Study design Number of uveal melanoma patients Number of first-line treatments (%) Number of surgically treated patients (%) Median time from metastasis to treatment months, (range) OS definition Median OS, published Kaplan-Meier estimate months, (95% CI) Median OS, digitised Kaplan-Meier estimate months, (95% CI) Region(s) Conventional chemotherapy (CHT) Dacarbazine Carling [1] 2015 Retrospective CCS * Thirteen patients received dacarbacine, five received temozolomide with or without interferon, five received fotemustine, two received carboplatin/dacarbacine/interferon-alpha/interleukin-2. Because of multiple different therapies the patients were included in the conventional chemotherapy group but could they could not be organised under a specific chemotherapy agent. * The Kaplan-Meier graph did not have steps and possibly because of resultant difficulty in digitizing the median survivals differ. † Median survival is 12 months when calculated from Table 1; the reported median survival of 15 months appears to correspond to mean survival [(7+8+8+12+16+18+20+29)/8=15 months]. ‡ The reported median survival of 18 months appears to be arithmetically calculated and not a Kaplan-Meier estimate. § Reported for all patients, not specifically for uveal melanoma patients.

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