PD-(L)1 immune checkpoint inhibitor-based regimens have recently expanded neoadjuvant and adjuvant treatment options for resectable non-small lung cell cancer (NSCLC). Dual immunotherapy has demonstrated long-term survival benefit in patients with metastatic NSCLC and promising clinical activity as neoadjuvant treatment in patients with resectable disease. This article presents the findings from the exploratory, concurrently randomised nivolumab plus ipilimumab and chemotherapy arms of the international phase III CheckMate 816 trial in patients with stage IB-IIIA resectable NSCLC.1
METHODS
Adults with stage IB-IIIA resectable NSCLC were treated with either three cycles of nivolumab administered biweekly plus one cycle of ipilimumab or three cycles of chemotherapy (administered on day 1 or days 1 and 8 of each 3-week cycle), followed by surgical resection. Analyses included event-free survival (EFS), overall survival (OS), pathological response, surgical outcomes, and safety profiles.
RESULTS
A total of 221 patients were concurrently randomised to nivolumab plus ipilimumab (N = 113) or chemotherapy (N = 108). After a median follow-up of 49.2 months, the median EFS was 54.8 months for nivolumab plus ipilimumab vs 20.9 months for chemotherapy (HR[95% CI]: 0.77[0.51-1.15]). The 3-year EFS rates were 56% and 44%, respectively. Although higher rates of EFS events were observed early in the nivolumab plus ipilimumab group, long-term benefit favoured this treatment. The 3-year OS rates were 73% with nivolumab plus ipilimumab vs 61% with chemotherapy (HR[95% CI]: 0.73[0.47-1.14]). Higher pathological complete response rates were observed with nivolumab plus ipilimumab compared to chemotherapy (20.4% vs 4.6%). Definitive surgery was performed in 83 patients (74%) in the nivolumab plus ipilimumab group and 82 patients (76%) in the chemotherapy group. Grade 3-4 treatment-related adverse events occurred in 14% of patients receiving nivolumab plus ipilimumab compared to 36% receiving chemotherapy.
CONCLUSIONS
Neoadjuvant nivolumab plus ipilimumab demonstrated potential long-term clinical benefit compared to chemotherapy, with trends toward improved survival and higher rates of pathological complete response. While EFS curves initially crossed during the preoperative phase, long-term results favoured nivolumab plus ipilimumab.
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