Elsevier

Clinical Lung Cancer

Volume 19, Issue 3, May 2018, Pages e349-e358
Clinical Lung Cancer

Original Study
Real-world Efficacy and Safety of Nivolumab for Advanced Non–Small-cell Lung Cancer: A Retrospective Multicenter Analysis

https://doi.org/10.1016/j.cllc.2018.01.001Get rights and content

Abstract

Background

Nivolumab, an immune checkpoint inhibitor, is now a standard treatment for previously treated advanced non–small-cell lung cancer based on the results from phase III clinical trials. We evaluated the real-world efficacy and safety of nivolumab in a nonselected population and identified the clinical characteristics that influence efficacy.

Materials and Methods

A total of 142 patients with advanced non–small-cell lung cancer who were administered nivolumab at Keio University and affiliated hospitals in Japan from January to July 2016 were enrolled. The treatment efficacy and adverse events were retrospectively reviewed, and the clinical characteristics associated with the nivolumab response were evaluated using univariate and stratified analyses and the Cochran-Mantel-Haenszel test.

Results

The objective response rate was 17.0% (95% confidence interval [CI], 12.0%-24.0%), the median progression-free survival (PFS) was 58 days (95% CI, 50-67 days), and the proportion of patients with adverse events of any grade was 45.0%. EGFR/ALK mutation status was inversely associated with the treatment response (P < .05), and the difference in PFS for the mutation-positive versus mutation-negative patients was statistically significant (49 vs. 63 days; hazard ratio, 1.9; 95% CI, 1.1-5.2; P = .029). Previous radiotherapy also had a positive association with the treatment response (P = .012).

Conclusion

The objective response rate, PFS, and adverse event profiles were comparable to those observed in previous clinical trials. EGFR/ALK mutation-negative status and previous radiotherapy might be key clinical characteristics associated with a positive treatment response. Our findings could aid in the efficient immunotherapeutic management of lung cancer.

Introduction

Lung cancer is the leading cause of cancer-related deaths worldwide. Most patients with advanced cancer develop relapse with chemotherapy-resistant disease after the administration of conventional cytotoxic agents. Today, immune checkpoint inhibitors have revolutionized cancer therapy and are recognized as a novel treatment option for patients with advanced cancer.1, 2 Nivolumab, an immunoglobulin G4 monoclonal antagonist antibody to programmed cell death protein 1, is now approved as a standard treatment for patients with advanced non–small-cell lung cancer (NSCLC) who have experienced disease progression during or after initial therapy with platinum-based doublet chemotherapy.3, 4

The efficacy and safety of nivolumab are based on the results from clinical trials conducted in carefully selected patient populations. These clinical trials enrolled relatively young patients with a good Eastern Cooperative Oncology Group (ECOG) performance status (PS) and excluded patients with complicated comorbidities, such as interstitial pneumonia (IP), autoimmune disease, and symptomatic central nervous system (CNS) metastases. The real-world efficacy and safety of nivolumab in nonselected populations remain unclear. We conducted a retrospective multicenter analysis of 142 nonselected patients with advanced NSCLC in Japan. We evaluated the real-world efficacy and safety of nivolumab in a nonselected population and identified the clinical characteristics that influence efficacy.

Section snippets

Study Population

A total of 142 previously treated advanced NSCLC patients, who had been administered nivolumab at Keio University and its 13 affiliated hospitals (the Keio Lung Oncology Group) from January to July 2016, were enrolled. Patients with a histologic or cytologic diagnosis of NSCLC, who had experienced disease progression during or after their initial treatment, were eligible for the present his study. In addition to patients with stage IIIB-IV disease and postoperative recurrence, patients with

Clinical Characteristics of Study Population

A total of 142 patients with stage IIIA-IV disease and postoperative recurrence were enrolled. The baseline clinical characteristics of the patients are summarized in Table 1. The median age was 67 years (range, 34-85 years), with 38 patients (26.8%) aged ≥ 75 years. Of the 142 patients, 106 (74.6%) were men and 36 (25.4%) were women. The ECOG PS was 0 for 43 patients (30.3%), 1 for 76 patients (53.5%), 2 for 15 patients (10.6%), and 3 for 8 patients (5.6%). The histologic subtypes included

Discussion

In the present retrospective multicenter study of 142 patients with advanced NSCLC, we have demonstrated the real-world efficacy and safety of nivolumab, a newly approved immune checkpoint inhibitor. We also identified the clinical characteristics that were significantly associated with an objective response. In the CheckMate 017 (squamous NSCLC)4 and CheckMate 057 (nonsquamous NSCLC)3 clinical trials, the ORR was 20.0% and 19.0% and the median PFS was 3.5 and 2.3 months, respectively. Although

Conclusion

In our retrospective analysis of 142 nonselected patients with advanced NSCLC, we have demonstrated the real-world efficacy and safety of nivolumab. EGFR/ALK mutation status and previous radiotherapy are key clinical characteristics that were significantly associated statistically with the efficacy of nivolumab. Nivolumab might be more effective in patients with an EGFR/ALK mutation-negative status or previous radiotherapy and be safe, regardless of patient age or the number of previous lines

Disclosure

K.S. has received honoraria from Chugai, Ono, Eli Lilly, AstraZeneca, Boehringer Ingelheim, and Shionogi. The remaining authors declare that they have no competing interests.

Acknowledgments

We wish to thank Kazumi Nishio (Kawasaki City Ida Hospital, Kanagawa, Japan), Fumitake Saito (Eiju General Hospital, Tokyo, Japan), Yusuke Suzuki (Kitasato Institute Hospital, Tokyo, Japan), and Akira Umeda (International Medical Welfare College Shioya Hospital, Tochigi, Japan) for assisting in data collection, and all members of the Keio Lung Oncology Group who participated in this study. This study was funded by Ono Pharmaceutical, Co., Ltd., and Chugai Pharmaceutical, Co., Ltd.

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