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

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.

Trial registration: ClinicalTrials.gov NCT01454102.

Conflict of interest statement

Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

© 2016 by American Society of Clinical Oncology.

Figures

Fig 1.

Characteristics of response in patients with advanced non–small-cell lung cancer treated with nivolumab monotherapy. Data are based on a March 2015 database lock. (A) Percent change in target lesion tumor burden from baseline over time. Only includes patients with baseline target lesion and one or more postbaseline target lesion assessments with nonmissing value (n = 49). Horizontal lines denote 30% decrease, 20% increase, and no change. (B) Best percent change in target lesion tumor burden from baseline. Only includes patients with baseline target lesion and one or more postbaseline target lesion assessments with nonmissing value (n = 49). Maximum percent reductions in target lesion tumor burden from baseline across all tumor assessments before subsequent therapy are used. Positive change in tumor burden indicates tumor growth; negative change in tumor burden indicates tumor reduction. Horizontal lines denote 30% decrease and 20% increase. Not all reductions of ≥ 30% from baseline are partial responses (ie, decrease in target lesion tumor burden but new or progressive nontarget lesions). (C) Time to and duration of response. CR, complete response; DOR, duration of response.

Fig 2.

Kaplan-Meier curves of progression-free survival (PFS) and overall survival (OS) by histology in patients with advanced non–small-cell lung cancer (NSCLC) treated with nivolumab monotherapy. (A) OS by NSCLC histology. Data for OS are based on an August 2015 database lock. (B) PFS by NSCLC histology. Data for PFS are based on a March 2015 database lock. Symbols denote censored observations.