Five-Year Survival and Correlates Among Patients With Advanced Melanoma, Renal Cell Carcinoma, or Non-Small Cell Lung Cancer Treated With Nivolumab.

This secondary analysis of the phase 1 CA209-003 clinical trial assesses the 5-year survival and other related factors among patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer receiving nivolumab. Key PointsQuestionWhat is the 5-year survival, and what factors are associated with 5-year survival among patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer receiving nivolumab? FindingsIn this secondary analysis of 270 patients from the CA209-003 clinical trial with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer, 5-year survival was negatively associated with presence of bone or liver metastases and positively associated with Eastern Cooperative Oncology Group performance status of 0, objective response, degree of tumor burden reduction, and adverse event occurrence. MeaningNivolumab treatment may be associated with durable survival among some heavily pretreated patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer; characterizing factors associated with long-term survival may guide future anti-programmed cell death 1-based clinical trial design. ImportanceNivolumab, a monoclonal antibody that inhibits programmed cell death 1, is approved by the US Food and Drug Administration for treating advanced melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and other malignancies. Data on long-term survival among patients receiving nivolumab are limited. ObjectivesTo analyze long-term overall survival (OS) among patients receiving nivolumab and identify clinical and laboratory measures associated with tumor regression and OS. Design, Setting, and ParticipantsThis was a secondary analysis of the phase 1 CA209-003 trial (with expansion cohorts), which was conducted at 13 US medical centers and included 270 patients with advanced melanoma, RCC, or NSCLC who received nivolumab and were enrolled between October 30, 2008, and December 28, 2011. The analyses were either specified in the original protocol or included in subsequent protocol amendments that were implemented between 2008 and 2012. Statistical analysis was performed from October 30, 2008, to November 11, 2016. InterventionIn the CA209-003 trial, patients received nivolumab (0.1-10.0 mg/kg) every 2 weeks in 8-week cycles for up to 96 weeks, unless they developed progressive disease, achieved a complete response, experienced unacceptable toxic effects, or withdrew consent. Main Outcomes and MeasuresSafety and activity of nivolumab; OS was a post hoc end point with a minimum follow-up of 58.3 months. ResultsOf 270 patients included in this analysis, 107 (39.6%) had melanoma (72 [67.3%] male; median age, 61 [range, 29-85] years), 34 (12.6%) had RCC (26 [76.5%] male; median age, 58 [range, 35-74] years), and 129 (47.8%) had NSCLC (79 [61.2%] male; median age, 65 [range, 38-85] years). Overall survival curves showed estimated 5-year rates of 34.2% among patients with melanoma, 27.7% among patients with RCC, and 15.6% among patients with NSCLC. In a multivariable analysis, the presence of liver (odds ratio [OR], 0.31; 95% CI, 0.12-0.83; P=.02) or bone metastases (OR, 0.31; 95% CI, 0.10-0.93; P=.04) was independently associated with reduced likelihood of survival at 5 years, whereas an Eastern Cooperative Oncology Group performance status of 0 (OR, 2.74; 95% CI, 1.43-5.27; P=.003) was independently associated with an increased likelihood of 5-year survival. Overall survival was significantly longer among patients with treatment-related AEs of any grade (median, 19.8 months; 95% CI, 13.8-26.9 months) or grade 3 or more (median, 20.3 months; 95% CI, 12.5-44.9 months) compared with those without treatment-related AEs (median, 5.8 months; 95% CI, 4.6-7.8 months) (P<.001 for both comparisons based on hazard ratios). Conclusions and RelevanceNivolumab treatment was associated with long-term survival in a subset of heavily pretreated patients with advanced melanoma, RCC, or NSCLC. Characterizing factors associated with long-term survival may inform treatment approaches and strategies for future clinical trial development. Trial RegistrationClinicalTrials.gov identifier: NCT00730639