Discontinuation of immune checkpoint inhibitor (ICI) above 18months of treatment in real-life patients with advanced non-small cell lung cancer (NSCLC): INTEPI, a multicentric retrospective study.

Abstract

The optimal treatment duration of ICIs for patients with advanced NSCLC remains uncertain. In phase 3 clinical trials, treatment continued for 2years or until disease progression with similar long-term survival rates. Real-life data are missing. This academic multicentric retrospective study aims at analyzing the characteristics of patients who discontinued treatment after at least 18months of ICI monotherapy, in the setting of controlled disease. Of the 1127 patients treated with immunotherapy in the given period in six centers, 107 patients had their tumor controlled after at least 18months of treatment and 54 (50%) of them had discontinued ICI. The median duration of treatment was 26months. Treatment was stopped due to prescriber choice or toxicity in 46% and 22% of cases, respectively. After a median follow-up of 21months from ICI discontinuation (95% CI 15.0-26.1months), 18 (33%) patients experienced tumor progression after a median time of 10.0months (range 2-33). From discontinuation, 12-month overall survival (OS) and progression-free survival (PFS) were 90% (95% CI 77.7-95.7) and 71% (95% CI 56.8-81.5), respectively; 24-month OS and PFS were 84% (95% CI 68.7-92.2) and 63% (95% CI 46.1-76.2), respectively. Duration of disease control after ICI discontinuation was correlated with tumor response at treatment discontinuation: PFS rate at 12months was 76% after complete response (CR n = 11) or partial response (PR n = 37) and 22% after only stable disease (SD n = 6) as best response, p-value = 0.0002. PFS rate at 12months was 80% for CR and/or complete metabolic response with 18F-FDG PET/CT (CMR) and 65% for others. Fourteen patients out of the 18 relapse patients received a subsequent treatment: seven with ICI rechallenge (best response 14% PR and 86% SD) and five with localized therapy with 60% CR. This real-life study provides new insight into long-term outcomes of patients with advanced NSCLC treated with ICI for at least 18months before treatment discontinuation in the absence of PD. Tumor response and CMR with FDG PET just before therapy discontinuation may be a predictive factor of prolonged disease control upon discontinuation. These results call for caution in discontinuing treatment in patients with stable disease as the best response.