Retrospective Efficacy Analysis of Immune Checkpoint Inhibitor Rechallenge in Patients with Non-Small Cell Lung Cancer.

Yuki Katayama,Yusuke Chihara,Takayuki Takeda,Junji Uchino,Osamu Hiranuma,Takahiro Yamada,Tadaaki Yamada,Takayuki Shimamoto,Koichi Takayama,Masahiro Iwasaku,Yoshiko Kaneko,Shinsuke Shiotsu

doi:10.3390/jcm9010102

Abstract

Little is known regarding the effectiveness and tolerability of immune checkpoint inhibitor (ICI) rechallenge after disease progression following initial ICI treatments. To identify eligible patients for ICI rechallenge, we retrospectively analyzed the relationship between clinical profiles and the effect of ICI rechallenge in patients with non-small cell lung cancer (NSCLC). We enrolled 35 NSCLC patients at six different institutions who were retreated with ICIs after discontinued initial ICI treatments due to disease progression. Cox proportional hazards models were used to assess the impact of clinical profiles on overall survival (OS) and progression-free survival (PFS). Median PFS and OS were 81 d (95% confidence interval, CI, 41–112 d) and 225 d (95% CI 106–361 d), respectively. The objective response rate was 2.9%, and the disease control rate was 42.9%. Multivariate analysis demonstrated that Eastern Cooperative Oncology Group Performance Score (ECOG-PS) ≥ 2 (hazard ratio, HR, 2.38; 95% CI 1.03–5.52; p = 0.043) and body mass index (BMI) > 20 (HR 0.43, 95% CI 0.19–0.95, p = 0.036) were significantly associated with PFS of ICI rechallenge. Our observations suggest that poor ECOG-PS and low BMI at intervention with ICI rechallenge may be negative predictors for ICI rechallenge treatment in patients with NSCLC.

Highlights

Lung cancer is the leading cause of cancer death worldwide [1]
Of the current immune checkpoint inhibitors (ICIs), nivolumab, pembrolizumab, atezolizumab, and durvalumab have been approved in the United States, Japan, and other countries for the treatment of patients with non-small cell lung cancer (NSCLC) based on phase III clinical trials [2,3,4,5,6]
A total of 35 NSCLC patients treated with ICI rechallenge between April 2017 and November 2018 at six different institutions in Japan were enrolled

Summary

Introduction

Current clinical studies have shown that some types of molecularly targeted therapies are able to successfully treat a subset of patients with advanced non-small cell lung cancer (NSCLC). The majority of patients with NSCLC acquire resistance to ICI treatments. After acquiring resistance to several therapeutic regimens, ICI rechallenge is considered to be one of the therapeutic options for patients with recurrent NSCLC. ICI rechallenge treatment has been clinically effective in only a small number of NSCLC patients. Previous retrospective studies regarding ICI rechallenge have analyzed only limited numbers of NSCLC patients [7,8]. In an effort to identify the patients eligible for ICI rechallenge treatment, we retrospectively analyzed the relationship between the clinical profiles and the effect of ICI rechallenge in patients with NSCLC

Results

Discussion

Conclusion