Metastatic site as a predictor of nivolumab efficacy in patients with advanced non-small cell lung cancer: A retrospective multicenter trial.

Motohiro Tamiya,Toru Kumagai,Kazumi Nishino,Akihiro Tamiya,Shinji Atagi,Kei Kunimasa,Hidekazu Suzuki,Takako Inoue,Takayuki Shiroyama,Madoka Kimura,Fumio Imamura,Tomonori Hirashima,Yoshihiko Taniguchi,Shun-Ichi Isa,Kenji Nakahama,Aamir Ahmad

doi:10.1371/journal.pone.0192227

Abstract

PurposeTo conduct a retrospective multicenter trial to determine the significance of metastatic site as a predictor of nivolumab efficacy in patients with advanced non-small cell lung cancer.MethodsThis study was conducted across three medical centers in Japan. We retrospectively reviewed all patients who commenced nivolumab treatment at these centers between December 17, 2015 and July 31, 2016. Clinical data were collected, including age, sex, smoking status, Eastern Cooperative Oncology Group performance status, and metastatic site (lymph nodes, liver, brain, bone, lungs [intrapulmonary metastasis], and malignant pleural effusion) at the time of commencing nivolumab treatment. Patients were followed-up until March 31, 2017.ResultsTwo hundred and one patients were enrolled. The median age at the time of commencing nivolumab treatment was 68 (range, 27–87) years. One hundred and thirty-five patients were male, 157 patients had a history of smoking, 153 patients had a performance status of 0–1, and 42 patients had squamous cell carcinoma. The median progression-free survival of all patients was 2.5 months. In the univariate analysis, a performance status of ≥2 (hazard ratio [HR]: 1.89, 95.0% confidence interval [CI]: 1.33–2.69; p < 0.001) and liver (HR: 2.09, 95.0% CI: 1.35–3.25; p < 0.001) and lung (HR: 1.57, 95.0% CI: 1.14–2.16; p < 0.01) metastases correlated with a significantly shorter progression-free survival in nivolumab-treated patients. In the multivariate analysis, a performance status of ≥2 (HR: 1.54, 95.0% CI: 1.05–2.25; p < 0.05) and liver (HR: 1.90, 95.0% CI: 1.21–2.98; p < 0.01) and lung (HR: 1.41, 95.0% CI: 1.00–1.99; p < 0.05) metastases were independently correlated with a significantly shorter progression-free survival in nivolumab-treated patients.ConclusionLiver and lung metastases and a poor performance status are independent predictors of nivolumab efficacy in patients with advanced non-small cell lung cancer.

Highlights

Lung cancer is the leading cause of cancer-related deaths worldwide [1]
One hundred and thirty-five patients were male, 157 patients had a history of smoking, 153 patients had a performance status of 0–1, and 42 patients had squamous cell carcinoma
A performance status of !2 and liver (HR: 2.09, 95.0% confidence intervals (CIs): 1.35–3.25; p < 0.001) and lung (HR: 1.57, 95.0% CI: 1.14–2.16; p < 0.01) metastases correlated with a significantly shorter progression-free survival in nivolumabtreated patients

Summary

Introduction

Effective treatments have been limited for patients with non-small cell lung cancer (NSCLC) whose disease progresses after first- or second-line chemotherapy. Newer agents (e.g., pemetrexed) have better side effect profiles and have shown non-inferiority to docetaxel. These agents have not demonstrated superiority to docetaxel with respect to overall survival when used as a second-line treatment [4]. Combined docetaxel and ramucirumab, a fully humanized immunoglobulin G1 monoclonal antibody that binds with high affinity to the extracellular domain of vascular endothelial growth factor receptor 2, has been shown to improve survival compared with docetaxel alone as a second-line chemotherapy [5].

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Conclusion