Long-term Outcomes among Patients Who Respond within the First Year to Nivolumab plus Ipilimumab or Nivolumab Monotherapy: A Pooled Analysis in 935 Patients
Menée à partir de données de trois essais incluant un total de 935 patients atteints d'un mélanome de stade avancé, cette étude évalue l'efficacité, du point de vue de la survie sans progression et la survie globale à 5 ans, du nivolumab seul ou en combinaison avec l'ipilimumab
Résumé en anglais
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 nonresponder 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 nonresponders 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.
