In the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab.,Here, we report 6.5-year efficacy and safety outcomes.,Patients with previously untreated unresectable stage III or stage IV melanoma were randomly assigned 1:1:1 to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks (n = 314), nivolumab 3 mg/kg once every 2 weeks (n = 316), or ipilimumab 3 mg/kg once every 3 weeks (four doses; n = 315).,Coprimary end points were progression-free survival and overall survival (OS) with nivolumab plus ipilimumab or nivolumab versus ipilimumab.,Secondary end points included objective response rate, descriptive efficacy assessments of nivolumab plus ipilimumab versus nivolumab alone, and safety.,Melanoma-specific survival (MSS; descriptive analysis), which excludes deaths unrelated to melanoma, was also evaluated.,Median OS (minimum follow-up, 6.5 years) was 72.1, 36.9, and 19.9 months in the combination, nivolumab, and ipilimumab groups, respectively.,Median MSS was not reached, 58.7, and 21.9 months, respectively; 6.5-year OS rates were 57%, 43%, and 25% in patients with BRAF-mutant tumors and 46%, 42%, and 22% in those with BRAF-wild-type tumors, respectively.,In patients who discontinued treatment, the median treatment-free interval was 27.6, 2.3, and 1.9 months, respectively.,Since the 5-year analysis, no new safety signals were observed.,These 6.5-year CheckMate 067 results, which include the longest median OS in a phase III melanoma trial reported to date and the first report of MSS, showed durable, improved clinical outcomes with nivolumab plus ipilimumab or nivolumab versus ipilimumab in patients with advanced melanoma and, in descriptive analyses, with the combination over nivolumab monotherapy.
This retrospective study aimed to identify prognostic factors in patients with brain metastases from cutaneous melanoma.,In all, 265 patients under regular screening according to valid national surveillance guidelines were included in the study.,Kaplan-Meier analyses were performed to estimate and to compare overall survival.,Cox modeling was used to identify independent determinants of the overall survival, which were used in explorative classification and regression tree analysis to define meaningful prognostic groups.,In total, 55.5% of our patients presented with two or less brain metastases, 82.6% had concurrent extracranial metastasis and 64% were asymptomatic and diagnosed during surveillance scans.,In all, 36.7% were candidates for local treatment (neurosurgery or stereotactic radiosurgery (SRS)).,The median overall survival of the entire collective was 5.0 months (95% confidence interval: 4.3-5.7).,Favourable independent prognostic factors were: normal pre-treatment level of serum lactate dehydrogenase (P<0.001), administered therapy (neurosurgery or SRS vs other, P=0.002), number of brain metastases (single vs multiple, P=0.032) and presence of bone metastasis (false vs true, P=0.044).,Three prognostic groups with significantly different overall survival were identified.,Candidates for local treatment (group I) had the longer median survival (9 months).,Remaining patients could be further classified in two groups on the basis of serum lactate dehydrogenase.,Applied treatment and serum lactate dehydrogenase levels were independent predictors of survival of patients with brain metastases from cutaneous melanoma.,Patients receiving local therapy have overall survival comparable with general stage IV melanoma patients.