PMID- 34648948
OWN - NLM
STAT- MEDLINE
DCOM- 20220223
LR  - 20220531
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 17
IP  - 2
DP  - 2022 Feb
TI  - First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the 
      Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial.
PG  - 289-308
LID - S1556-0864(21)03207-X [pii]
LID - 10.1016/j.jtho.2021.09.010 [doi]
AB  - 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.
CI  - Copyright (c) 2021 International Association for the Study of Lung Cancer. 
      Published by Elsevier Inc. All rights reserved.
FAU - Paz-Ares, Luis G
AU  - Paz-Ares LG
AD  - Hospital Universitario 12 de Octubre, H12O-CNIO Lung Cancer Clinical Research 
      Unit, Universidad Complutense & CiberOnc, Madrid, Spain. Electronic address: 
      lpazaresr@seom.org.
FAU - Ramalingam, Suresh S
AU  - Ramalingam SS
AD  - Winship Cancer Institute, Emory University, Atlanta, Georgia.
FAU - Ciuleanu, Tudor-Eliade
AU  - Ciuleanu TE
AD  - Institutul Oncologic Prof Dr Ion Chiricuta and UMF Iuliu Hatieganu, Cluj Napoca, 
      Romania.
FAU - Lee, Jong-Seok
AU  - Lee JS
AD  - Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
FAU - Urban, Laszlo
AU  - Urban L
AD  - Matrai Gyogyintezet, Matrahaza, Hungary.
FAU - Caro, Reyes Bernabe
AU  - Caro RB
AD  - Hospital Universitario Virgen Del Rocio, Instituto de Biomedicina de Seville, 
      Seville, Spain.
FAU - Park, Keunchil
AU  - Park K
AD  - Samsung Medical Center at Sungkyunkwan University School of Medicine, Seoul, 
      Republic of Korea.
FAU - Sakai, Hiroshi
AU  - Sakai H
AD  - Saitama Cancer Center, Saitama, Japan.
FAU - Ohe, Yuichiro
AU  - Ohe Y
AD  - National Cancer Center Hospital, Tokyo, Japan.
FAU - Nishio, Makoto
AU  - Nishio M
AD  - Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, 
      Japan.
FAU - Audigier-Valette, Clarisse
AU  - Audigier-Valette C
AD  - Hopital Sainte Musse, Toulon, France.
FAU - Burgers, Jacobus A
AU  - Burgers JA
AD  - Netherlands Cancer Institute, Amsterdam, The Netherlands.
FAU - Pluzanski, Adam
AU  - Pluzanski A
AD  - Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
FAU - Sangha, Randeep
AU  - Sangha R
AD  - Cross Cancer Institute, Edmonton, Alberta, Canada.
FAU - Gallardo, Carlos
AU  - Gallardo C
AD  - Fundacion Arturo Lopez Perez, Santiago, Chile.
FAU - Takeda, Masayuki
AU  - Takeda M
AD  - Kindai University Faculty of Medicine, Osaka, Japan.
FAU - Linardou, Helena
AU  - Linardou H
AD  - Metropolitan Hospital, Neo Faliro, Greece.
FAU - Lupinacci, Lorena
AU  - Lupinacci L
AD  - Hospital Italiano De Buenos Aires, Buenos Aires, Argentina.
FAU - Lee, Ki Hyeong
AU  - Lee KH
AD  - Chungbuk National University Hospital, Cheongju-si, Republic of Korea.
FAU - Caserta, Claudia
AU  - Caserta C
AD  - Santa Maria Hospital, Terni, Italy.
FAU - Provencio, Mariano
AU  - Provencio M
AD  - Hosp. Univ. Puerta De Hierro-IDIPHIM, Universidad Autonoma de Madrid, Madrid, 
      Spain.
FAU - Carcereny, Enric
AU  - Carcereny E
AD  - Catalan Institute of Oncology-Germans Trias i Pujol Hospital, B-ARGO group, 
      Badalona, Spain.
FAU - Otterson, Gregory A
AU  - Otterson GA
AD  - The Ohio State University, Columbus, Ohio.
FAU - Schenker, Michael
AU  - Schenker M
AD  - SF. Nectarie Oncology Center, Craiova, Romania.
FAU - Zurawski, Bogdan
AU  - Zurawski B
AD  - Ambulatorium Chemioterapii, Bydgoszcz, Poland.
FAU - Alexandru, Aurelia
AU  - Alexandru A
AD  - Institute of Oncology "Prof. Dr. Alexandru Trestioreanu" Bucha, Bucharest, 
      Romania.
FAU - Vergnenegre, Alain
AU  - Vergnenegre A
AD  - Limoges University Hospital, Limoges, France.
FAU - Raimbourg, Judith
AU  - Raimbourg J
AD  - ICO Rene Gauducheau, St Herblain, France.
FAU - Feeney, Kynan
AU  - Feeney K
AD  - St John of God Hospital Murdoch, Perth, Australia.
FAU - Kim, Sang-We
AU  - Kim SW
AD  - Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of 
      Korea.
FAU - Borghaei, Hossein
AU  - Borghaei H
AD  - Fox Chase Cancer Center, Philadelphia, Pennsylvania.
FAU - O'Byrne, Kenneth John
AU  - O'Byrne KJ
AD  - Queensland University of Technology, Princess Alexandra Hospital, Brisbane, 
      Australia.
FAU - Hellmann, Matthew D
AU  - Hellmann MD
AD  - Memorial Sloan Kettering Cancer Center, New York, New York.
FAU - Memaj, Arteid
AU  - Memaj A
AD  - Bristol Myers Squibb, Princeton, New Jersey.
FAU - Nathan, Faith Ellen
AU  - Nathan FE
AD  - Bristol Myers Squibb, Princeton, New Jersey.
FAU - Bushong, Judith
AU  - Bushong J
AD  - Bristol Myers Squibb, Princeton, New Jersey.
FAU - Tran, Phuong
AU  - Tran P
AD  - Bristol Myers Squibb, Princeton, New Jersey.
FAU - Brahmer, Julie R
AU  - Brahmer JR
AD  - Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland.
FAU - Reck, Martin
AU  - Reck M
AD  - Airway Research Center North, German Center for Lung Research, LungClinic, 
      Grosshansdorf, Germany.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20211012
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - 0 (Ipilimumab)
RN  - 31YO63LBSN (Nivolumab)
SB  - IM
CIN - J Thorac Oncol. 2022 Feb;17(2):176-178. PMID: 35074222
MH  - Adult
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Humans
MH  - Ipilimumab/adverse effects
MH  - *Lung Neoplasms/pathology
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - *Nivolumab/adverse effects
OTO - NOTNLM
OT  - CTLA-4
OT  - First-line
OT  - Immunotherapy
OT  - Metastatic non-small cell lung cancer
OT  - PD-1 checkpoint inhibitor
EDAT- 2021/10/15 06:00
MHDA- 2022/02/24 06:00
CRDT- 2021/10/14 20:14
PHST- 2021/06/30 00:00 [received]
PHST- 2021/09/07 00:00 [revised]
PHST- 2021/09/20 00:00 [accepted]
PHST- 2021/10/15 06:00 [pubmed]
PHST- 2022/02/24 06:00 [medline]
PHST- 2021/10/14 20:14 [entrez]
AID - S1556-0864(21)03207-X [pii]
AID - 10.1016/j.jtho.2021.09.010 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2022 Feb;17(2):289-308. doi: 10.1016/j.jtho.2021.09.010. Epub 
      2021 Oct 12.