TY - JOUR
T1 - Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer
AU - CheckMate 816 Investigators
AU - Forde, Patrick M.
AU - Spicer, Jonathan
AU - Lu, Shun
AU - Provencio, Mariano
AU - Mitsudomi, Tetsuya
AU - Awad, Mark M.
AU - Felip, Enriqueta
AU - Broderick, Stephen R.
AU - Brahmer, Julie R.
AU - Swanson, Scott J.
AU - Kerr, Keith
AU - Wang, Changli
AU - Ciuleanu, Tudor Eliade
AU - Saylors, Gene B.
AU - Tanaka, Fumihiro
AU - Ito, Hiroyuki
AU - Chen, Ke Neng
AU - Liberman, Moishe
AU - Vokes, Everett E.
AU - Taube, Janis M.
AU - Dorange, Cecile
AU - Cai, Junliang
AU - Fiore, Joseph
AU - Jarkowski, Anthony
AU - Balli, David
AU - Sausen, Mark
AU - Pandya, Dimple
AU - Calvet, Christophe Y.
AU - Girard, Nicolas
N1 - Publisher Copyright:
Copyright © 2022 Massachusetts Medical Society.
PY - 2022/5/26
Y1 - 2022/5/26
N2 - Background: Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non-small-cell lung cancer (NSCLC). In early-phase trials, nivolumabbased neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings. Methods: In this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum- based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients. Results: The median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P = 0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-pluschemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group. Conclusions: In patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery.
AB - Background: Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non-small-cell lung cancer (NSCLC). In early-phase trials, nivolumabbased neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings. Methods: In this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum- based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients. Results: The median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P = 0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-pluschemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group. Conclusions: In patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery.
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U2 - 10.1056/NEJMoa2202170
DO - 10.1056/NEJMoa2202170
M3 - Article
C2 - 35403841
AN - SCOPUS:85130221027
SN - 0028-4793
VL - 386
SP - 1973
EP - 1985
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 21
ER -