Display options
Cite
Paz-Ares LG, Ramalingam SS, Ciuleanu TE, et al. First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial. J Thorac Oncol. 2021;doi: 10.1016/j.jtho.2021.09.010.
Paz-Ares, L. G., Ramalingam, S. S., Ciuleanu, T. E., Lee, J. S., Urban, L., Caro, R. B., Park, K., Sakai, H., Ohe, Y., Nishio, M., Audigier-Valette, C., Burgers, J. A., Pluzanski, A., Sangha, R., Gallardo, C., Takeda, M., Linardou, H., Lupinacci, L., Lee, K. H., Caserta, C., Provencio, M., Carcereny, E., Otterson, G. A., Schenker, M., Zurawski, B., Alexandru, A., Vergnenegre, A., Raimbourg, J., Feeney, K., Kim, S. W., Borghaei, H., O'Byrne, K. J., Hellmann, M. D., Memaj, A., Nathan, F. E., Bushong, J., Tran, P., Brahmer, J. R., & Reck, M. (2021). First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, . https://doi.org/10.1016/j.jtho.2021.09.010
Paz-Ares, Luis G, et al. "First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer vol. (2021). doi: https://doi.org/10.1016/j.jtho.2021.09.010
Paz-Ares LG, Ramalingam SS, Ciuleanu TE, Lee JS, Urban L, Caro RB, Park K, Sakai H, Ohe Y, Nishio M, Audigier-Valette C, Burgers JA, Pluzanski A, Sangha R, Gallardo C, Takeda M, Linardou H, Lupinacci L, Lee KH, Caserta C, Provencio M, Carcereny E, Otterson GA, Schenker M, Zurawski B, Alexandru A, Vergnenegre A, Raimbourg J, Feeney K, Kim SW, Borghaei H, O'Byrne KJ, Hellmann MD, Memaj A, Nathan FE, Bushong J, Tran P, Brahmer JR, Reck M. First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial. J Thorac Oncol. 2021 Oct 12; doi: 10.1016/j.jtho.2021.09.010. Epub 2021 Oct 12. PMID: 34648948.
Copy Download .nbib Format: NLM
Share it on

J Thorac Oncol. 2021 Oct 12; doi: 10.1016/j.jtho.2021.09.010. Epub 2021 Oct 12.

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

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

Luis G Paz-Ares, Suresh S Ramalingam, Tudor-Eliade Ciuleanu, Jong-Seok Lee, Laszlo Urban, Reyes Bernabe Caro, Keunchil Park, Hiroshi Sakai, Yuichiro Ohe, Makoto Nishio, Clarisse Audigier-Valette, Jacobus A Burgers, Adam Pluzanski, Randeep Sangha, Carlos Gallardo, Masayuki Takeda, Helena Linardou, Lorena Lupinacci, Ki Hyeong Lee, Claudia Caserta, Mariano Provencio, Enric Carcereny, Gregory A Otterson, Michael Schenker, Bogdan Zurawski, Aurelia Alexandru, Alain Vergnenegre, Judith Raimbourg, Kynan Feeney, Sang-We Kim, Hossein Borghaei, Kenneth John O'Byrne, Matthew D Hellmann, Arteid Memaj, Faith Ellen Nathan, Judith Bushong, Phuong Tran, Julie R Brahmer, Martin Reck

Affiliations

  1. Hospital Universitario 12 de Octubre, H12O-CNIO Lung Cancer Clinical Research Unit, Universidad Complutense & CiberOnc, Madrid, Spain. Electronic address: [email protected].
  2. Winship Cancer Institute, Emory University, Atlanta, Georgia.
  3. Institutul Oncologic Prof Dr Ion Chiricuta and UMF Iuliu Hatieganu, Cluj Napoca, România.
  4. Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
  5. Matrai Gyogyintezet, Matrahaza, Hungary.
  6. Hospital Universitario Virgen Del Rocio, Instituto de Biomedicina de Seville, Seville, Spain.
  7. Samsung Medical Center at Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
  8. Saitama Cancer Center, Saitama, Japan.
  9. National Cancer Center Hospital, Tokyo, Japan.
  10. Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
  11. Hôpital Sainte Musse, Toulon, France.
  12. Netherlands Cancer Institute, Amsterdam, The Netherlands.
  13. Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
  14. Cross Cancer Institute, Edmonton, Alberta, Canada.
  15. Fundacion Arturo Lopez Perez, Santiago, Chile.
  16. Kindai University Faculty of Medicine, Osaka, Japan.
  17. Metropolitan Hospital, Neo Faliro, Greece.
  18. Hospital Italiano De Buenos Aires, Buenos Aires, Argentina.
  19. Chungbuk National University Hospital, Cheongju-si, Republic of Korea.
  20. Santa Maria Hospital, Terni, Italy.
  21. Hosp. Univ. Puerta De Hierro-IDIPHIM, Universidad Autónoma de Madrid, Madrid, Spain.
  22. Catalan Institute of Oncology-Germans Trias i Pujol Hospital, B-ARGO group, Badalona, Spain.
  23. The Ohio State University, Columbus, Ohio.
  24. SF. Nectarie Oncology Center, Craiova, Romania.
  25. Ambulatorium Chemioterapii, Bydgoszcz, Poland.
  26. Institute of Oncology "Prof. Dr. Alexandru Trestioreanu" Bucha, Bucharest, Romania.
  27. Limoges University Hospital, Limoges, France.
  28. ICO Rene Gauducheau, St Herblain, France.
  29. St John of God Hospital Murdoch, Perth, Australia.
  30. Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  31. Fox Chase Cancer Center, Philadelphia, Pennsylvania.
  32. Queensland University of Technology, Princess Alexandra Hospital, Brisbane, Australia.
  33. Memorial Sloan Kettering Cancer Center, New York, New York.
  34. Bristol Myers Squibb, Princeton, New Jersey.
  35. Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland.
  36. Airway Research Center North, German Center for Lung Research, LungClinic, Grosshansdorf, Germany.

PMID: 34648948 DOI: 10.1016/j.jtho.2021.09.010

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.

Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Keywords: CTLA-4; First-line; Immunotherapy; Metastatic non–small cell lung cancer; PD-1 checkpoint inhibitor

Publication Types