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.
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    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)",
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    issn = "1556-0864",
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    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

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