KEY TAKEAWAYS
- The phase III trial aimed to determine whether neoadjuvant nivolumab plus chemotherapy improves event-free survival in resectable stage II–IIIb NSCLC pts compared to neoadjuvant placebo plus chemotherapy.
- The primary endpoint was EFS. Secondary endpoints were pCR and MPR, OS, and safety.
- The study demonstrated significantly improved event-free survival and a favorable safety profile in resectable NSCLC pts compared to neoadjuvant chemotherapy alone.
While neoadjuvant(neoadj) nivolumab (NIVO) + chemotherapy(chemo) has shown efficacy benefits over chemo alone in resectable non-small cell lung cancer (NSCLC) patients(pts), the effectiveness of perioperative NIVO + chemo remains unexplored in phase 3 studies.
Researchers aimed to determine whether neoadj NIVO plus chemo improves event-free survival in resectable stage II–IIIb NSCLC pts compared to neoadj placebo plus chemo.
Adults with untreated resectable stage IIA (>4 cm)–IIIB (N2) NSCLC (AJCC v8), EGFR/ALK wild-type, and ECOG PS ≤1 were randomized 1:1. They were stratified by tumor histology, PD-L1 expression, and disease stage. The two arms included NIVO 360 mg Q3W + platinum-doublet chemo (4 cycles) followed by surgery and adjuvant NIVO 480 mg Q4W (1 year), or placebo Q3W + platinum-doublet chemo (4 cycles) followed by surgery and adjuvant placebo Q4W (1 year). The primary endpoint was EFS (RECIST v1.1 per BICR), and secondary endpoints included pCR and MPR (both per BIPR), OS, and safety.
The result demonstrated that the baseline characteristics were balanced between arms (NIVO + chemo/NIVO, n = 229; chemo/PBO, n = 232). With a minimum follow-up of 15.7 months, NIVO + chemo/NIVO significantly improved EFS compared to chemo/PBO (median [95% CI], not reached [28.9 months–not reached] vs 18.4 months [13.6–28.1]; HR [97.36% CI], 0.58 [0.42–0.81]; P = 0.00025).
NIVO + chemo/NIVO also demonstrated enhanced pCR rates (25.3% vs 4.7%; odds ratio, 6.64 [95% CI, 3.40–12.97]) and MPR rates (35.4% vs 12.1%; odds ratio: 4.01 [2.48–6.49]) compared to chemo/PBO. Definitive surgery rates were 78% vs 77% in the NIVO + chemo/NIVO vs chemo/PBO arms; 89% vs 90% were R0 resections, respectively. Grade 3–4 treatment-related AEs were 32% and 25% in the NIVO + chemo/NIVO and chemo/PBO arms; surgery-related AEs were 12% and 12%, respectively.
The study demonstrated significantly improved event-free survival and a favorable safety profile in resectable NSCLC pts compared to neoadjuvant chemotherapy alone.
Clinical Trial: https://clinicaltrials.gov/study/NCT04025879
Cascone T, Awad MM, Spicer JD, He J, Lu S, Sepesi B, Tanaka F, Taube JM, Cornelissen R, Havel L, Kuzdzal J, Petruzelka LB, Wu L, Pujol J, Ito H, Coronado Erdmann C, Sathyanarayana P, Meadows-Shropshire S, Provencio Pulla M. Annals of Oncology (2023) 34 (suppl_2): S1254-S1335. 10.1016/annonc/annonc1358.
