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J Clin Oncol. 2016 Sep 1;34(25):2969-79. doi: 10.1200/JCO.2016.66.9861. Epub 2016 Jun 27.

Nivolumab in Combination With Platinum-Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer.

Author information

1
Naiyer A. Rizvi and Matthew D. Hellmann, Memorial Sloan Kettering Cancer Center, New York, NY; Julie R. Brahmer, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Rosalyn A. Juergens, Juravinski Cancer Centre at McMaster University, Hamilton; Scott A. Laurie, Ottawa Hospital Cancer Centre, Ottawa; Frances A. Shepherd, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hossein Borghaei, Fox Chase Cancer Center, Philadelphia, PA; Scott Gettinger, Yale Cancer Center, New Haven, CT; Laura Q. Chow, University of Washington, Seattle, WA; David E. Gerber, University of Texas Southwestern Medical Center, Dallas, TX; Jonathan W. Goldman, University of California, Los Angeles, Los Angeles, CA; Allen C. Chen, Yun Shen, Faith E. Nathan, and Christopher T. Harbison, Bristol-Myers Squibb, Princeton, NJ; and Scott Antonia, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. nar2144@cumc.columbia.edu.
2
Naiyer A. Rizvi and Matthew D. Hellmann, Memorial Sloan Kettering Cancer Center, New York, NY; Julie R. Brahmer, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Rosalyn A. Juergens, Juravinski Cancer Centre at McMaster University, Hamilton; Scott A. Laurie, Ottawa Hospital Cancer Centre, Ottawa; Frances A. Shepherd, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hossein Borghaei, Fox Chase Cancer Center, Philadelphia, PA; Scott Gettinger, Yale Cancer Center, New Haven, CT; Laura Q. Chow, University of Washington, Seattle, WA; David E. Gerber, University of Texas Southwestern Medical Center, Dallas, TX; Jonathan W. Goldman, University of California, Los Angeles, Los Angeles, CA; Allen C. Chen, Yun Shen, Faith E. Nathan, and Christopher T. Harbison, Bristol-Myers Squibb, Princeton, NJ; and Scott Antonia, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.

Abstract

PURPOSE:

Nivolumab, a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody, has demonstrated improved survival in previously treated patients with advanced non-small-cell lung cancer (NSCLC). CheckMate 012, a phase I, multicohort study, was conducted to explore the safety and efficacy of nivolumab as monotherapy or combined with current standard therapies in first-line advanced NSCLC. Here, we report results for nivolumab plus platinum-based doublet chemotherapy (PT-DC).

PATIENTS AND METHODS:

Patients (N = 56) received nivolumab (intravenously) plus PT-DC concurrently every 3 weeks for four cycles followed by nivolumab alone until progression or unacceptable toxicity. Regimens were nivolumab 10 mg/kg plus gemcitabine-cisplatin (squamous) or pemetrexed-cisplatin (nonsquamous) or nivolumab 5 or 10 mg/kg plus paclitaxel-carboplatin (all histologies). The primary objective was to assess safety and tolerability. Secondary objectives included objective response rate and 24-week progression-free survival rate (per Response Evaluation Criteria in Solid Tumors version 1.1); exploratory objectives included overall survival (OS) and response by tumor programmed death ligand-1 expression.

RESULTS:

No dose-limiting toxicities occurred during the first 6 weeks of treatment. Forty-five percent of patients (25 of 56 patients) reported grade 3 or 4 treatment-related adverse events (AEs); 7% of patients (n = 4) had pneumonitis. Twenty-one percent of patients (n = 12) discontinued all study therapy as a result of treatment-related AEs. Objective response rates for nivolumab 10 mg/kg plus gemcitabine-cisplatin, nivolumab 10 mg/kg plus pemetrexed-cisplatin, nivolumab 10 mg/kg plus paclitaxel-carboplatin, and nivolumab 5 mg/kg plus paclitaxel-carboplatin were 33%, 47%, 47%, and 43%, respectively; 24-week progression-free survival rates were 51%, 71%, 38%, and 51%, respectively; 2-year OS rates were 25%, 33%, 27%, and 62%, respectively. Responses were achieved regardless of tumor programmed death ligand-1 expression.

CONCLUSION:

The safety profile of nivolumab plus PT-DC was consistent with that expected for individual agents; however, treatment discontinuation related to AEs was greater with the combination. Encouraging activity was observed, especially for the nivolumab 5 mg/kg plus paclitaxel-carboplatin group, with a 2-year OS rate of 62%.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01454102.

PMID:
27354481
PMCID:
PMC5569693
DOI:
10.1200/JCO.2016.66.9861
[Indexed for MEDLINE]
Free PMC Article

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