Surgical outcomes from the phase 3 CheckMate 816 trial: Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo alone as neoadjuvant treatment for patients with resectable non-small cell lung cancer (NSCLC).
Authors: Jonathan Spicer, Changli Wang, Fumihiro Tanaka, Gene Brian Saylors, Ke-Neng Chen, Moishe Liberman, Everett E. Vokes, Nicolas Girard, Shun Lu, Mariano Provencio, Tetsuya Mitsudomi, Mark M. Awad, Enriqueta Felip, Patrick M. Forde, Scott Swanson, Julie R. Brahmer, Keith Kerr, Cécile Dorange, Junliang Cai, Stephen Broderick
Journal: Journal of Clinical Oncology (2021)

8503 Background: CheckMate 816 (NCT02998528) is a randomized phase 3 study of neoadjuvant NIVO + chemo vs chemo in resectable NSCLC. The study met its first primary endpoint, demonstrating significantly improved pathological complete response (pCR) with neoadjuvant NIVO + chemo. Here we report key surgical outcomes from the study. Methods: Adults with stage IB (≥ 4 cm)–IIIA (per AJCC 7 th ed) resectable NSCLC, ECOG PS ≤ 1, and no known EGFR/ ALK alterations were randomized to NIVO 360 mg + platinum-doublet chemo Q3W or chemo Q3W for 3 cycles (n = 179 each). Definitive surgery was to be performed within 6 weeks of treatment. Primary endpoints are pCR (defined as 0% viable tumor cells in lung and lymph nodes) and event-free survival; both are evaluated by blinded independent review. Feasibility of surgery and surgery-related adverse events (AEs) are exploratory endpoints. Results: Baseline characteristics were comparable between arms; 64% of patients (pts) were stage IIIA. Definitive surgery rates were 83% with NIVO + chemo (n = 149) vs 75% with chemo (n = 135). Reasons for cancelled surgery were disease progression (12 and 17 pts, respectively), AEs (2 pts/arm), or other scenarios (14 and 19 pts, respectively; including pt refusal, unresectability, poor lung function). Minimally invasive surgery rates were 30% and 22%, and conversion from minimally invasive to open surgery rates were 11% and 16% for NIVO + chemo and chemo, respectively. Lobectomy was performed in 77% vs 61% of pts, and pneumonectomy in 17% and 25% for NIVO + chemo vs chemo, respectively. AEs were responsible for delays of surgery in 6 pts in the NIVO + chemo arm and 9 pts in the chemo arm. An R0 resection was achieved in 83% vs 78% of pts and median residual viable tumor (RVT) cells in the primary tumor bed were 10% vs 74% for NIVO + chemo vs chemo. There was no increase in median (Q1, Q3) duration of surgery and length of hospitalization between NIVO + chemo vs chemo (184 [130, 252] vs 217 [150, 283] min; and 10.0 [7, 14] vs 10.0 [7, 14] days, respectively). Any-grade and grade 3–4 surgery-related AEs were reported in 41% vs 47% and 11% vs 15% of the NIVO + chemo vs chemo arms, respectively. Grade 5 surgery-related AEs were reported in 2 vs 0 pts in the NIVO + chemo vs chemo arms; 0 vs 3 pts died due to treatment-related AEs, respectively. Conclusions: In CheckMate 816, neoadjuvant NIVO + chemo did not impede the feasibility and timing of surgery, nor the extent or completeness of resection vs chemo alone; treatment was tolerable and did not increase surgical complications. NIVO + chemo led to increased depth of pathological response. The surgical outcome data from CheckMate 816 along with significant improvement in pCR support NIVO + chemo as a potential neoadjuvant option for patients with stage IB to IIIA resectable NSCLC. Clinical trial information: NCT02998528.