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First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial

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Abstract
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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.

Keywords: CTLA-4; First-line; Immunotherapy; Metastatic non?small cell lung cancer; PD-1 checkpoint inhibitor.
Author(s)
김상위Adam PluzanskiAlain VergnenegreArteid MemajAurelia AlexandruBogdan ZurawskiCarlos GallardoClarisse Audigier-ValetteClaudia CasertaEnric CarcerenFaith Ellen NathanGregory A OttersonHelena LinardouHiroshi SakaiHossein BorghaeiJacobus A BurgersJong-Seok LeeJudith BushongJudith R
Issued Date
2021
Type
Article
Keyword
CTLA-4First-lineImmunotherapyMetastatic non?small cell lung cancerPD-1 checkpoint inhibitor.
DOI
10.1016/j.jtho.2021.09.010
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8436
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2582819215&amp;context=PC&amp;vid=ULSAN&amp;lang=ko_KR&amp;search_scope=default_scope&amp;adaptor=primo_central_multiple_fe&amp;tab=default_tab&amp;query=any,contains,First-Line%20Nivolumab%20Plus%20Ipilimumab%20in%20Advanced%20NSCLC:%204-Year%20Outcomes%20From%20the%20Randomized,%20Open-Label,%20Phase%203%20CheckMate%20227%20Part%201%20Trial&amp;pcAvailability=true
Publisher
Journal of Thoracic Oncology
Location
미국
Language
영어
ISSN
1556-0864
Citation Volume
1556
Citation Number
21
Citation Start Page
03207
Citation End Page
03207
Appears in Collections:
Medicine > Medicine
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