First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial
- Authors
- Paz-Ares, L.G.[Paz-Ares, L.G.]; Ramalingam, S.S.[Ramalingam, S.S.]; Ciuleanu, T.-E.[Ciuleanu, T.-E.]; Lee, J.-S.[Lee, J.-S.]; Urban, L.[Urban, L.]; Caro, R.B.[Caro, R.B.]; Park, K.[Park, K.]; Sakai, H.[Sakai, H.]; Ohe, Y.[Ohe, Y.]; Nishio, M.[Nishio, M.]; Audigier-Valette, C.[Audigier-Valette, C.]; Burgers, J.A.[Burgers, J.A.]; Pluzanski, A.[Pluzanski, A.]; Sangha, R.[Sangha, R.]; Gallardo, C.[Gallardo, C.]; Takeda, M.[Takeda, M.]; Linardou, H.[Linardou, H.]; Lupinacci, L.[Lupinacci, L.]; Lee, K.H.[Lee, K.H.]; Caserta, C.[Caserta, C.]; Provencio, M.[Provencio, M.]; Carcereny, E.[Carcereny, E.]; Otterson, G.A.[Otterson, G.A.]; Schenker, M.[Schenker, M.]; Zurawski, B.[Zurawski, B.]; Alexandru, A.[Alexandru, A.]; Vergnenegre, A.[Vergnenegre, A.]; Raimbourg, J.[Raimbourg, J.]; Feeney, K.[Feeney, K.]; Kim, S.-W.[Kim, S.-W.]; Borghaei, H.[Borghaei, H.]; O'Byrne, K.J.[O'Byrne, K.J.]; Hellmann, M.D.[Hellmann, M.D.]; Memaj, A.[Memaj, A.]; Nathan, F.E.[Nathan, F.E.]; Bushong, J.[Bushong, J.]; Tran, P.[Tran, P.]; Brahmer, J.R.[Brahmer, J.R.]; Reck, M.[Reck, M.]
- Issue Date
- Feb-2022
- Publisher
- Elsevier Inc.
- Keywords
- CTLA-4; First-line; Immunotherapy; Metastatic non–small cell lung cancer; PD-1 checkpoint inhibitor
- Citation
- Journal of Thoracic Oncology, v.17, no.2, pp.289 - 308
- Indexed
- SCIE
SCOPUS
- Journal Title
- Journal of Thoracic Oncology
- Volume
- 17
- Number
- 2
- Start Page
- 289
- End Page
- 308
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/92633
- DOI
- 10.1016/j.jtho.2021.09.010
- ISSN
- 1556-0864
- Abstract
- Introduction: In CheckMate 227, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with tumor programmed death-ligand 1 (PD-L1) greater than or equal to 1% (primary end point) or less than 1% (prespecified descriptive analysis). We report results with minimum 4 years' follow-up. Methods: Adults with previously untreated stage IV or recurrent NSCLC were randomized (1:1:1) to nivolumab plus ipilimumab, nivolumab, or chemotherapy (PD-L1 ≥1%); or to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 <1%). Efficacy included OS and other measures. Safety included timing and management of immune-mediated adverse events (AEs). A post hoc analysis evaluated efficacy in patients who discontinued nivolumab plus ipilimumab due to treatment-related AEs (TRAEs). Results: After 54.8 months' median follow-up, OS remained longer with nivolumab plus ipilimumab versus chemotherapy in patients with PD-L1 greater than or equal to 1% (hazard ratio = 0.76; 95% confidence interval: 0.65–0.90) and PD-L1 less than 1% (0.64; 0.51–0.81); 4-year OS rate with nivolumab plus ipilimumab versus chemotherapy was 29% versus 18% (PD-L1 ≥1%); and 24% versus 10% (PD-L1 <1%). Benefits were observed in both squamous and nonsquamous histologies. In a descriptive analysis, efficacy was improved with nivolumab plus ipilimumab relative to nivolumab (PD-L1 ≥1%) and nivolumab plus chemotherapy (PD-L1 <1%). Safety was consistent with previous reports. The most common immune-mediated AE with nivolumab plus ipilimumab, nivolumab, and nivolumab plus chemotherapy was rash; most immune-mediated AEs (except endocrine events) occurred within 6 months from start of treatment and resolved within 3 months after, mainly with systemic corticosteroids. Patients who discontinued nivolumab plus ipilimumab due to TRAEs had long-term OS benefits, as seen in the all randomized population. Conclusions: At more than 4 years' minimum follow-up, with all patients off immunotherapy treatment for at least 2 years, first-line nivolumab plus ipilimumab continued to demonstrate durable long-term efficacy in patients with advanced NSCLC. No new safety signals were identified. Immune-mediated AEs occurred early and resolved quickly with guideline-based management. Discontinuation of nivolumab plus ipilimumab due to TRAEs did not have a negative impact on the long-term benefits seen in all randomized patients. © 2021 International Association for the Study of Lung Cancer
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