Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis

H Borghaei; T-E Ciuleanu; J-S Lee; A Pluzanski; R Bernabe Caro; M Gutierrez; Y Ohe; M Nishio; J Goldman; N Ready; D R Spigel; S S Ramalingam; L G Paz-Ares; J F Gainor; S Ahmed; M Reck; M Maio; K J O'Byrne; A Memaj; F Nathan; P Tran; M D Hellmann; J R Brahmer

doi:10.1016/j.annonc.2022.11.006

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis

Ann Oncol. 2023 Feb;34(2):173-185. doi: 10.1016/j.annonc.2022.11.006. Epub 2022 Nov 19.

Authors

H Borghaei¹, T-E Ciuleanu², J-S Lee³, A Pluzanski⁴, R Bernabe Caro⁵, M Gutierrez⁶, Y Ohe⁷, M Nishio⁸, J Goldman⁹, N Ready¹⁰, D R Spigel¹¹, S S Ramalingam¹², L G Paz-Ares¹³, J F Gainor¹⁴, S Ahmed¹⁵, M Reck¹⁶, M Maio¹⁷, K J O'Byrne¹⁸, A Memaj¹⁹, F Nathan²⁰, P Tran²¹, M D Hellmann²², J R Brahmer²³

Affiliations

¹ Hematology and Oncology Department, Fox Chase Cancer Center, Philadelphia, USA. Electronic address: hossein.borghaei@fccc.edu.
² Department of Medical Oncology, Institutul Oncologic Prof Dr Ion Chiricuta, Cluj-Napoca; Department of Medical Oncology, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania.
³ Department of Hematology/Oncology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
⁴ Department of Lung Cancer and Chest Tumours, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
⁵ Medical Oncology Department, Hospital Universitario Virgen Del Rocio, Instituto de Biomedicina de Seville, Seville, Spain.
⁶ John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, USA.
⁷ Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
⁸ Department of Thoracic Medical Oncology Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
⁹ David Geffen School of Medicine, UCLA, Los Angeles.
¹⁰ Department of Medicine, Duke University School of Medicine, Durham.
¹¹ Thoracic Medical Oncology, Sarah Cannon Research Institute/Tennessee Oncology PLCC, Nashville.
¹² Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA.
¹³ Medical Oncology Department, Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain.
¹⁴ Department of Medicine, Massachusetts General Hospital, Boston, USA.
¹⁵ Department of Medical Oncology, University Hospitals of Leicester, Leicester, UK.
¹⁶ Department of Thoracic Oncology, Airway Research Center North, German Center for Lung Research, Lung Clinic, Grosshansdorf, Germany.
¹⁷ Center for Immuno-Oncology, University Hospital of Siena and University of Siena, Siena, Italy.
¹⁸ Princess Alexandra Hospital, Translational Research Institute and Queensland University of Technology, Brisbane, Australia.
¹⁹ Global Biometrics and Data Sciences, Bristol Myers Squibb, Princeton.
²⁰ OneClinical, Bristol Myers Squibb, Princeton.
²¹ WW Medical Oncology Department, Bristol Myers Squibb, Princeton.
²² Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York.
²³ Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Kimmel Cancer Center, Baltimore, USA.

PMID: 36414192
DOI: 10.1016/j.annonc.2022.11.006

Abstract

Background: First-line nivolumab plus ipilimumab prolongs survival versus chemotherapy in advanced non-small-cell lung cancer (NSCLC). We further characterized clinical benefit with this regimen in a large pooled patient population and assessed the effect of response on survival.

Patients and methods: Data were pooled from four studies of first-line nivolumab plus ipilimumab in advanced NSCLC (CheckMate 227 Part 1, 817 cohort A, 568 Part 1, and 012). Overall survival (OS), progression-free survival (PFS), objective response rate, duration of response, and safety were assessed. Landmark analyses of OS by response status at 6 months and by tumor burden reduction in responders to nivolumab plus ipilimumab were also assessed.

Results: In the pooled population (N = 1332) with a minimum follow-up of 29.1-58.9 months, median OS was 18.6 months, with a 3-year OS rate of 35%; median PFS was 5.4 months (3-year PFS rate, 17%). Objective response rate was 36%; median duration of response was 23.7 months, with 38% of responders having an ongoing response at 3 years. In patients with tumor programmed death-ligand 1 (PD-L1) <1%, ≥1%, 1%-49%, or ≥50%, 3-year OS rates were 30%, 38%, 30%, and 48%. Three-year OS rates were 30% and 38% in patients with squamous or non-squamous histology. Efficacy outcomes in patients aged ≥75 years were similar to the overall pooled population (median OS, 20.1 months; 3-year OS rate, 34%). In the pooled population, responders to nivolumab plus ipilimumab at 6 months had longer post-landmark OS than those with stable or progressive disease; 3-year OS rates were 66%, 22%, and 14%, respectively. Greater depth of response was associated with prolonged survival; in patients with tumor burden reduction ≥80%, 50% to <80%, or 30% to <50%, 3-year OS rates were 85%, 72%, and 44%, respectively. No new safety signals were identified in the pooled population.

Conclusion: Long-term survival benefit and durable response with nivolumab plus ipilimumab in this large patient population further support this first-line treatment option for advanced NSCLC.

Keywords: NSCLC; dual immunotherapy; ipilimumab; nivolumab.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / adverse effects
Carcinoma, Non-Small-Cell Lung* / pathology
Humans
Ipilimumab / adverse effects
Lung Neoplasms* / pathology
Nivolumab / therapeutic use
Progression-Free Survival

Substances

Nivolumab
Ipilimumab