Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer

Scott Gettinger, Naiyer A. Rizvi, Laura Q. Chow, Hossein Borghaei, Julie Brahmer, Neal Ready, David E. Gerber, Frances A. Shepherd, Scott Antonia, Jonathan W. Goldman, Rosalyn A. Juergens, Scott A. Laurie, Faith E. Nathan, Yun Shen, Christopher T. Harbison, Matthew D. Hellmann

Research output: Contribution to journalArticle

214 Citations (Scopus)

Abstract

Purpose Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non-small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial. Methods Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment was permitted per protocol. The primary objective was to assess safety; secondary objectives included objective response rate (ORR) and 24-week progression-free survival (PFS) rate; overall survival (OS) was an exploratory end point. Results Any-grade treatment-related adverse events (AEs) occurred in 71% of patients, most commonly: fatigue (29%), rash (19%), nausea (14%), diarrhea (12%), pruritus (12%), and arthralgia (10%). Ten patients (19%) reported grade 3 to 4 treatment-related AEs; grade 3 rash was the only grade 3 to 4 event occurring in more than one patient (n = 2; 4%). Six patients (12%) discontinued because of a treatment-related AE. The confirmed ORR was 23% (12 of 52), including four ongoing complete responses. Nine of 12 responses (75%) occurred by first tumor assessment (week 11); eight (67%) were ongoing (range, 5.3+ to 25.8+ months) at the time of data lock. ORR was 28% (nine of 32) in patients with any degree of tumor PD-ligand 1 expression and 14% (two of 14) in patients with no PD-ligand 1 expression. Median PFS was 3.6 months, and the 24-week PFS rate was 41% (95% CI, 27 to 54). Median OS was 19.4 months, and the 1-year and 18-month OS rates were 73% (95% CI, 59 to 83) and 57% (95% CI, 42 to 70), respectively. Conclusion First-line nivolumab monotherapy demonstrated a tolerable safety profile and durable responses in first-line advanced NSCLC.

Original languageEnglish (US)
Pages (from-to)2980-2987
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number25
DOIs
StatePublished - Sep 1 2016

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Non-Small Cell Lung Carcinoma
Disease-Free Survival
Survival Rate
docetaxel
Exanthema
Therapeutics
Survival
Ligands
Safety
Arthralgia
Pruritus
nivolumab
Nausea
Fatigue
Diarrhea
Neoplasms
Antibodies

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Gettinger, S., Rizvi, N. A., Chow, L. Q., Borghaei, H., Brahmer, J., Ready, N., ... Hellmann, M. D. (2016). Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. Journal of Clinical Oncology, 34(25), 2980-2987. https://doi.org/10.1200/JCO.2016.66.9929

Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. / Gettinger, Scott; Rizvi, Naiyer A.; Chow, Laura Q.; Borghaei, Hossein; Brahmer, Julie; Ready, Neal; Gerber, David E.; Shepherd, Frances A.; Antonia, Scott; Goldman, Jonathan W.; Juergens, Rosalyn A.; Laurie, Scott A.; Nathan, Faith E.; Shen, Yun; Harbison, Christopher T.; Hellmann, Matthew D.

In: Journal of Clinical Oncology, Vol. 34, No. 25, 01.09.2016, p. 2980-2987.

Research output: Contribution to journalArticle

Gettinger, S, Rizvi, NA, Chow, LQ, Borghaei, H, Brahmer, J, Ready, N, Gerber, DE, Shepherd, FA, Antonia, S, Goldman, JW, Juergens, RA, Laurie, SA, Nathan, FE, Shen, Y, Harbison, CT & Hellmann, MD 2016, 'Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer', Journal of Clinical Oncology, vol. 34, no. 25, pp. 2980-2987. https://doi.org/10.1200/JCO.2016.66.9929
Gettinger S, Rizvi NA, Chow LQ, Borghaei H, Brahmer J, Ready N et al. Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. Journal of Clinical Oncology. 2016 Sep 1;34(25):2980-2987. https://doi.org/10.1200/JCO.2016.66.9929
Gettinger, Scott ; Rizvi, Naiyer A. ; Chow, Laura Q. ; Borghaei, Hossein ; Brahmer, Julie ; Ready, Neal ; Gerber, David E. ; Shepherd, Frances A. ; Antonia, Scott ; Goldman, Jonathan W. ; Juergens, Rosalyn A. ; Laurie, Scott A. ; Nathan, Faith E. ; Shen, Yun ; Harbison, Christopher T. ; Hellmann, Matthew D. / Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 25. pp. 2980-2987.
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abstract = "Purpose Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non-small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial. Methods Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment was permitted per protocol. The primary objective was to assess safety; secondary objectives included objective response rate (ORR) and 24-week progression-free survival (PFS) rate; overall survival (OS) was an exploratory end point. Results Any-grade treatment-related adverse events (AEs) occurred in 71{\%} of patients, most commonly: fatigue (29{\%}), rash (19{\%}), nausea (14{\%}), diarrhea (12{\%}), pruritus (12{\%}), and arthralgia (10{\%}). Ten patients (19{\%}) reported grade 3 to 4 treatment-related AEs; grade 3 rash was the only grade 3 to 4 event occurring in more than one patient (n = 2; 4{\%}). Six patients (12{\%}) discontinued because of a treatment-related AE. The confirmed ORR was 23{\%} (12 of 52), including four ongoing complete responses. Nine of 12 responses (75{\%}) occurred by first tumor assessment (week 11); eight (67{\%}) were ongoing (range, 5.3+ to 25.8+ months) at the time of data lock. ORR was 28{\%} (nine of 32) in patients with any degree of tumor PD-ligand 1 expression and 14{\%} (two of 14) in patients with no PD-ligand 1 expression. Median PFS was 3.6 months, and the 24-week PFS rate was 41{\%} (95{\%} CI, 27 to 54). Median OS was 19.4 months, and the 1-year and 18-month OS rates were 73{\%} (95{\%} CI, 59 to 83) and 57{\%} (95{\%} CI, 42 to 70), respectively. Conclusion First-line nivolumab monotherapy demonstrated a tolerable safety profile and durable responses in first-line advanced NSCLC.",
author = "Scott Gettinger and Rizvi, {Naiyer A.} and Chow, {Laura Q.} and Hossein Borghaei and Julie Brahmer and Neal Ready and Gerber, {David E.} and Shepherd, {Frances A.} and Scott Antonia and Goldman, {Jonathan W.} and Juergens, {Rosalyn A.} and Laurie, {Scott A.} and Nathan, {Faith E.} and Yun Shen and Harbison, {Christopher T.} and Hellmann, {Matthew D.}",
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T1 - Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer

AU - Gettinger, Scott

AU - Rizvi, Naiyer A.

AU - Chow, Laura Q.

AU - Borghaei, Hossein

AU - Brahmer, Julie

AU - Ready, Neal

AU - Gerber, David E.

AU - Shepherd, Frances A.

AU - Antonia, Scott

AU - Goldman, Jonathan W.

AU - Juergens, Rosalyn A.

AU - Laurie, Scott A.

AU - Nathan, Faith E.

AU - Shen, Yun

AU - Harbison, Christopher T.

AU - Hellmann, Matthew D.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Purpose Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non-small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial. Methods Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment was permitted per protocol. The primary objective was to assess safety; secondary objectives included objective response rate (ORR) and 24-week progression-free survival (PFS) rate; overall survival (OS) was an exploratory end point. Results Any-grade treatment-related adverse events (AEs) occurred in 71% of patients, most commonly: fatigue (29%), rash (19%), nausea (14%), diarrhea (12%), pruritus (12%), and arthralgia (10%). Ten patients (19%) reported grade 3 to 4 treatment-related AEs; grade 3 rash was the only grade 3 to 4 event occurring in more than one patient (n = 2; 4%). Six patients (12%) discontinued because of a treatment-related AE. The confirmed ORR was 23% (12 of 52), including four ongoing complete responses. Nine of 12 responses (75%) occurred by first tumor assessment (week 11); eight (67%) were ongoing (range, 5.3+ to 25.8+ months) at the time of data lock. ORR was 28% (nine of 32) in patients with any degree of tumor PD-ligand 1 expression and 14% (two of 14) in patients with no PD-ligand 1 expression. Median PFS was 3.6 months, and the 24-week PFS rate was 41% (95% CI, 27 to 54). Median OS was 19.4 months, and the 1-year and 18-month OS rates were 73% (95% CI, 59 to 83) and 57% (95% CI, 42 to 70), respectively. Conclusion First-line nivolumab monotherapy demonstrated a tolerable safety profile and durable responses in first-line advanced NSCLC.

AB - Purpose Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non-small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial. Methods Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment was permitted per protocol. The primary objective was to assess safety; secondary objectives included objective response rate (ORR) and 24-week progression-free survival (PFS) rate; overall survival (OS) was an exploratory end point. Results Any-grade treatment-related adverse events (AEs) occurred in 71% of patients, most commonly: fatigue (29%), rash (19%), nausea (14%), diarrhea (12%), pruritus (12%), and arthralgia (10%). Ten patients (19%) reported grade 3 to 4 treatment-related AEs; grade 3 rash was the only grade 3 to 4 event occurring in more than one patient (n = 2; 4%). Six patients (12%) discontinued because of a treatment-related AE. The confirmed ORR was 23% (12 of 52), including four ongoing complete responses. Nine of 12 responses (75%) occurred by first tumor assessment (week 11); eight (67%) were ongoing (range, 5.3+ to 25.8+ months) at the time of data lock. ORR was 28% (nine of 32) in patients with any degree of tumor PD-ligand 1 expression and 14% (two of 14) in patients with no PD-ligand 1 expression. Median PFS was 3.6 months, and the 24-week PFS rate was 41% (95% CI, 27 to 54). Median OS was 19.4 months, and the 1-year and 18-month OS rates were 73% (95% CI, 59 to 83) and 57% (95% CI, 42 to 70), respectively. Conclusion First-line nivolumab monotherapy demonstrated a tolerable safety profile and durable responses in first-line advanced NSCLC.

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