KEY TAKEAWAYS
- The CheckMate-816 phase III trial explored potential differences in clinical outcomes between neoadjuvant N + ipi and chemo arms in the CheckMate 816 trial.
- The study measured EFS, pCR, OS, surgical outcomes, safety, and efficacy.
- The result demonstrated that N+I offered promising results in CheckMate 816, and chemo maintains its crown as a standard neoadjuvant treatment for resectable NSCLC.
CheckMate 816 proved nivolumab+ chemotherapy(N+C) tops standard chemo for early lung cancer in both tumor control and surgery-ready patients, boosting survival and shrinking tumors, but chemo remains the usual treatment for now.
Researchers aimed to explore potential differences in clinical outcomes between neoadjuvant N + ipilimumab(ipi) and C arms in the CheckMate 816 trial.
Adults with resectable non-small cell lung cancer (NSCLC) stages IB (≥ 4 cm)–IIIA (per AJCC 7th ed), ECOG PS ≤ 1, and no known EGFR/ALK mutations were randomly assigned to either 3 cycles of N 3 mg/kg Q2W + 1 cycle of I 1 mg/kg or 3 cycles of C Q3W. Enrollment to the N + I arm closed early based on evolving external trial data.
The study’s primary analysis population was changed to N + C vs. C. Assessments included event-free survival (EFS), pathological complete response (pCR), overall survival (OS), surgical outcomes, safety, and efficacy determined by a 4-gene inflammatory signature score (CD8A, STAT1, LAG3, and CD274 [PD-L1]) derived from RNA sequencing of baseline tumor samples.
In the N + I (n = 113) and C (n = 108) arms, baseline characteristics were generally balanced. At a median follow-up of 49.2 months (database lock, 14 Oct 2022), N + I showed favorable outcomes. Median EFS was 54.8 months vs. 20.9 months with N + I vs. C (HR 0.77 [95% CI 0.51–1.15]; 3-year EFS rates, 56% vs. 44%). Median OS was not reached (HR 0.73 [95% CI 0.47–1.14]; 3-year OS rates, 73% vs. 61%). N + I exhibited a higher pCR rate (95% CI) compared to C (20% [13.4–29.0] vs. 5% [1.5–10.5]).
Definitive surgery occurred for 74% and 76% of patients in the N + I and C arms; R0 resection rates were 80% and 71%. A high vs. low baseline 4-gene inflammatory score was associated with improved EFS and pCR with N + I.
Grade 3–4 treatment-related adverse events (TRAEs) and grade 3–4 surgery-related AEs were reported in 14% vs. 36% and 15% vs. 14% of patients in the N + I and C arms, respectively. Outcomes in key subgroups, including PD-L1 expression, will be presented.
The result demonstrated that N+I offered promising results in CheckMate 816, and chemo maintains its crown as a standard neoadjuvant treatment for resectable NSCLC.
Clinical Trial: https://clinicaltrials.gov/study/NCT02998528
Awad MM, Forde PM, Girard N, Spicer JD, Wang C, Lu S, Mitsudomi T, Felip E, Broderick S, Swanson SJ, Brahmer JR, Kerr KM, Saylors G, Chen K, Cai JL, Mahmood J, Neely J, Balli D, Hu N, Provencio Pulla M. Neoadjuvant nivolumab (N) + ipilimumab (I) vs chemotherapy (C) in the phase III CheckMate 816 trial. Ann Oncol. 2023;34(suppl_2):S732-S745. doi:10.1016/annonc/annonc1304.
