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