Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort

Neal E. Ready, Patrick A. Ott, Matthew D. Hellmann, Jon Zugazagoitia, Christine L. Hann, Filippo de Braud, Scott J. Antonia, Paolo A. Ascierto, Victor Moreno, Akin Atmaca, Stefania Salvagni, Matthew Taylor, Asim Amin, D. Ross Camidge, Leora Horn, Emiliano Calvo, Ang Li, Wen Hong Lin, Margaret K. Callahan, David R. Spigel

Research output: Contribution to journalArticle

Abstract

Introduction: Nivolumab monotherapy is approved in the United States for third-line or later metastatic small cell lung cancer based on pooled data from nonrandomized and randomized cohorts of the multicenter, open-label, phase 1/2 trial of nivolumab ± ipilimumab (CheckMate 032; NCT01928394). We report updated results, including long-term overall survival (OS), from the randomized cohort. Methods: Patients with small cell lung cancer and disease progression after one to two prior chemotherapy regimens were randomized 3:2 to nivolumab 3 mg/kg every 2 weeks or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four cycles followed by nivolumab 3 mg/kg every 2 weeks. Patients were stratified by number of prior chemotherapy regimens and treated until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by blinded independent central review. Results: Overall, 147 patients received nivolumab and 96 nivolumab plus ipilimumab. Minimum follow-up for ORR/progression-free survival/safety was 11.9 months (nivolumab) and 11.2 months (nivolumab plus ipilimumab). ORR increased with nivolumab plus ipilimumab (21.9% versus 11.6% with nivolumab; odds ratio: 2.12; 95% confidence interval: 1.06–4.26; p = 0.03). For long-term OS, minimum follow-up was 29.0 months (nivolumab) versus 28.4 months (nivolumab plus ipilimumab); median (95% confidence interval) OS was 5.7 (3.8–7.6) versus 4.7 months (3.1–8.3). Twenty-four–month OS rates were 17.9% (nivolumab) and 16.9% (nivolumab plus ipilimumab). Grade 3 to 4 treatment-related adverse event rates were 12.9% (nivolumab) versus 37.5% (nivolumab plus ipilimumab), and treatment-related deaths were n =1 versus n = 3, respectively. Conclusions: Whereas ORR (primary endpoint) was higher with nivolumab plus ipilimumab versus nivolumab, OS was similar between groups. In each group, OS remained encouraging with long-term follow-up. Toxicities were more common with combination therapy versus nivolumab monotherapy.

Original languageEnglish (US)
JournalJournal of Thoracic Oncology
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Small Cell Lung Carcinoma
Survival
ipilimumab
nivolumab
Disease Progression
Confidence Intervals
Drug Therapy

Keywords

  • Immunotherapy
  • Ipilimumab
  • Programmed death-1 inhibitor
  • Small cell lung cancer: Nivolumab

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer : Results From the CheckMate 032 Randomized Cohort. / Ready, Neal E.; Ott, Patrick A.; Hellmann, Matthew D.; Zugazagoitia, Jon; Hann, Christine L.; de Braud, Filippo; Antonia, Scott J.; Ascierto, Paolo A.; Moreno, Victor; Atmaca, Akin; Salvagni, Stefania; Taylor, Matthew; Amin, Asim; Camidge, D. Ross; Horn, Leora; Calvo, Emiliano; Li, Ang; Lin, Wen Hong; Callahan, Margaret K.; Spigel, David R.

In: Journal of Thoracic Oncology, 01.01.2019.

Research output: Contribution to journalArticle

Ready, NE, Ott, PA, Hellmann, MD, Zugazagoitia, J, Hann, CL, de Braud, F, Antonia, SJ, Ascierto, PA, Moreno, V, Atmaca, A, Salvagni, S, Taylor, M, Amin, A, Camidge, DR, Horn, L, Calvo, E, Li, A, Lin, WH, Callahan, MK & Spigel, DR 2019, 'Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort', Journal of Thoracic Oncology. https://doi.org/10.1016/j.jtho.2019.10.004
Ready, Neal E. ; Ott, Patrick A. ; Hellmann, Matthew D. ; Zugazagoitia, Jon ; Hann, Christine L. ; de Braud, Filippo ; Antonia, Scott J. ; Ascierto, Paolo A. ; Moreno, Victor ; Atmaca, Akin ; Salvagni, Stefania ; Taylor, Matthew ; Amin, Asim ; Camidge, D. Ross ; Horn, Leora ; Calvo, Emiliano ; Li, Ang ; Lin, Wen Hong ; Callahan, Margaret K. ; Spigel, David R. / Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer : Results From the CheckMate 032 Randomized Cohort. In: Journal of Thoracic Oncology. 2019.
@article{8aaebb13c3824907b49044880e0f808d,
title = "Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort",
abstract = "Introduction: Nivolumab monotherapy is approved in the United States for third-line or later metastatic small cell lung cancer based on pooled data from nonrandomized and randomized cohorts of the multicenter, open-label, phase 1/2 trial of nivolumab ± ipilimumab (CheckMate 032; NCT01928394). We report updated results, including long-term overall survival (OS), from the randomized cohort. Methods: Patients with small cell lung cancer and disease progression after one to two prior chemotherapy regimens were randomized 3:2 to nivolumab 3 mg/kg every 2 weeks or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four cycles followed by nivolumab 3 mg/kg every 2 weeks. Patients were stratified by number of prior chemotherapy regimens and treated until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by blinded independent central review. Results: Overall, 147 patients received nivolumab and 96 nivolumab plus ipilimumab. Minimum follow-up for ORR/progression-free survival/safety was 11.9 months (nivolumab) and 11.2 months (nivolumab plus ipilimumab). ORR increased with nivolumab plus ipilimumab (21.9{\%} versus 11.6{\%} with nivolumab; odds ratio: 2.12; 95{\%} confidence interval: 1.06–4.26; p = 0.03). For long-term OS, minimum follow-up was 29.0 months (nivolumab) versus 28.4 months (nivolumab plus ipilimumab); median (95{\%} confidence interval) OS was 5.7 (3.8–7.6) versus 4.7 months (3.1–8.3). Twenty-four–month OS rates were 17.9{\%} (nivolumab) and 16.9{\%} (nivolumab plus ipilimumab). Grade 3 to 4 treatment-related adverse event rates were 12.9{\%} (nivolumab) versus 37.5{\%} (nivolumab plus ipilimumab), and treatment-related deaths were n =1 versus n = 3, respectively. Conclusions: Whereas ORR (primary endpoint) was higher with nivolumab plus ipilimumab versus nivolumab, OS was similar between groups. In each group, OS remained encouraging with long-term follow-up. Toxicities were more common with combination therapy versus nivolumab monotherapy.",
keywords = "Immunotherapy, Ipilimumab, Programmed death-1 inhibitor, Small cell lung cancer: Nivolumab",
author = "Ready, {Neal E.} and Ott, {Patrick A.} and Hellmann, {Matthew D.} and Jon Zugazagoitia and Hann, {Christine L.} and {de Braud}, Filippo and Antonia, {Scott J.} and Ascierto, {Paolo A.} and Victor Moreno and Akin Atmaca and Stefania Salvagni and Matthew Taylor and Asim Amin and Camidge, {D. Ross} and Leora Horn and Emiliano Calvo and Ang Li and Lin, {Wen Hong} and Callahan, {Margaret K.} and Spigel, {David R.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.jtho.2019.10.004",
language = "English (US)",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",

}

TY - JOUR

T1 - Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer

T2 - Results From the CheckMate 032 Randomized Cohort

AU - Ready, Neal E.

AU - Ott, Patrick A.

AU - Hellmann, Matthew D.

AU - Zugazagoitia, Jon

AU - Hann, Christine L.

AU - de Braud, Filippo

AU - Antonia, Scott J.

AU - Ascierto, Paolo A.

AU - Moreno, Victor

AU - Atmaca, Akin

AU - Salvagni, Stefania

AU - Taylor, Matthew

AU - Amin, Asim

AU - Camidge, D. Ross

AU - Horn, Leora

AU - Calvo, Emiliano

AU - Li, Ang

AU - Lin, Wen Hong

AU - Callahan, Margaret K.

AU - Spigel, David R.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Introduction: Nivolumab monotherapy is approved in the United States for third-line or later metastatic small cell lung cancer based on pooled data from nonrandomized and randomized cohorts of the multicenter, open-label, phase 1/2 trial of nivolumab ± ipilimumab (CheckMate 032; NCT01928394). We report updated results, including long-term overall survival (OS), from the randomized cohort. Methods: Patients with small cell lung cancer and disease progression after one to two prior chemotherapy regimens were randomized 3:2 to nivolumab 3 mg/kg every 2 weeks or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four cycles followed by nivolumab 3 mg/kg every 2 weeks. Patients were stratified by number of prior chemotherapy regimens and treated until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by blinded independent central review. Results: Overall, 147 patients received nivolumab and 96 nivolumab plus ipilimumab. Minimum follow-up for ORR/progression-free survival/safety was 11.9 months (nivolumab) and 11.2 months (nivolumab plus ipilimumab). ORR increased with nivolumab plus ipilimumab (21.9% versus 11.6% with nivolumab; odds ratio: 2.12; 95% confidence interval: 1.06–4.26; p = 0.03). For long-term OS, minimum follow-up was 29.0 months (nivolumab) versus 28.4 months (nivolumab plus ipilimumab); median (95% confidence interval) OS was 5.7 (3.8–7.6) versus 4.7 months (3.1–8.3). Twenty-four–month OS rates were 17.9% (nivolumab) and 16.9% (nivolumab plus ipilimumab). Grade 3 to 4 treatment-related adverse event rates were 12.9% (nivolumab) versus 37.5% (nivolumab plus ipilimumab), and treatment-related deaths were n =1 versus n = 3, respectively. Conclusions: Whereas ORR (primary endpoint) was higher with nivolumab plus ipilimumab versus nivolumab, OS was similar between groups. In each group, OS remained encouraging with long-term follow-up. Toxicities were more common with combination therapy versus nivolumab monotherapy.

AB - Introduction: Nivolumab monotherapy is approved in the United States for third-line or later metastatic small cell lung cancer based on pooled data from nonrandomized and randomized cohorts of the multicenter, open-label, phase 1/2 trial of nivolumab ± ipilimumab (CheckMate 032; NCT01928394). We report updated results, including long-term overall survival (OS), from the randomized cohort. Methods: Patients with small cell lung cancer and disease progression after one to two prior chemotherapy regimens were randomized 3:2 to nivolumab 3 mg/kg every 2 weeks or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four cycles followed by nivolumab 3 mg/kg every 2 weeks. Patients were stratified by number of prior chemotherapy regimens and treated until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by blinded independent central review. Results: Overall, 147 patients received nivolumab and 96 nivolumab plus ipilimumab. Minimum follow-up for ORR/progression-free survival/safety was 11.9 months (nivolumab) and 11.2 months (nivolumab plus ipilimumab). ORR increased with nivolumab plus ipilimumab (21.9% versus 11.6% with nivolumab; odds ratio: 2.12; 95% confidence interval: 1.06–4.26; p = 0.03). For long-term OS, minimum follow-up was 29.0 months (nivolumab) versus 28.4 months (nivolumab plus ipilimumab); median (95% confidence interval) OS was 5.7 (3.8–7.6) versus 4.7 months (3.1–8.3). Twenty-four–month OS rates were 17.9% (nivolumab) and 16.9% (nivolumab plus ipilimumab). Grade 3 to 4 treatment-related adverse event rates were 12.9% (nivolumab) versus 37.5% (nivolumab plus ipilimumab), and treatment-related deaths were n =1 versus n = 3, respectively. Conclusions: Whereas ORR (primary endpoint) was higher with nivolumab plus ipilimumab versus nivolumab, OS was similar between groups. In each group, OS remained encouraging with long-term follow-up. Toxicities were more common with combination therapy versus nivolumab monotherapy.

KW - Immunotherapy

KW - Ipilimumab

KW - Programmed death-1 inhibitor

KW - Small cell lung cancer: Nivolumab

UR - http://www.scopus.com/inward/record.url?scp=85076529782&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85076529782&partnerID=8YFLogxK

U2 - 10.1016/j.jtho.2019.10.004

DO - 10.1016/j.jtho.2019.10.004

M3 - Article

C2 - 31629915

AN - SCOPUS:85076529782

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

SN - 1556-0864

ER -