Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients

Purpose: To investigate the predictive value of RECIST response within 3, 6, or 12 months on long-term survival, and explore differences between nivolumab+ipilimumab and nivolumab monotherapy, we analyzed pooled 5-year data of 935 responder and non-responder patients at various time points after treatment initiation in CheckMate 069, 066, and 067 studies. Patients and methods: Treatment-naive advanced melanoma patients received nivolumab+ipilimumab or nivolumab monotherapy. To decrease immortal time bias, 3-, 6-, or 12-month overall survival (OS) and progression-free survival (PFS) landmark analyses were performed. Association between characteristics and response was evaluated by univariate and multivariate analyses. Results: Response rates at any time were 58 % (239/409) for nivolumab+ipilimumab and 44 % (230/526) for nivolumab monotherapy. In 12-month landmark analyses, 5-year OS rates for responders versus non-responders were 82 % versus 40 % with nivolumab+ipilimumab (HR=0.23 [95 % CI, 0.15–0.35]) and 76 % versus 32 % with nivolumab monotherapy (HR=0.22 [95 % CI, 0.16–0.31]). PFS rates were 83 % versus 32 % and 69 % versus 46 %, respectively. Similar strong associations between response at 3 and 6 months and 5-year OS and PFS were also observed with more than 70 % of the responses observed in the first 3 months. Response rates correlated with baseline LDH and PD-L1 status by multivariate analysis but the association between response and long-term survival was maintained in landmark analyses even among patients with high LDH and low PD-L1 expression. Conclusion: Clinical response evaluated in the first months of therapy is a strong predictor of long-term survival, even in patients with poor prognostic biomarkers.