Efficacy and safety of immune checkpoint inhibitor rechallenge in non-small cell lung cancer: A systematic review and meta-analysis

Thorac Cancer. 2023 Sep;14(25):2536-2547. doi: 10.1111/1759-7714.15063. Epub 2023 Aug 8.

Abstract

Background: The aim of the study was to explore the efficacy and safety of immune checkpoint inhibitor (ICI) rechallenge in patients with non-small cell lung cancer (NSCLC).

Methods: Studies that enrolled NSCLC patients treated with two lines of ICIs were included using four databases. The initial line (1L-) and subsequent lines (2L-) of ICIs were defined as 1L-ICI and 2L-ICI, respectively.

Results: A total of 17 studies involving 2100 patients were included. The pooled objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) for 2L-ICIs were 10%, 50%, 3.0 months, and 13.1 months, respectively. The 2L-ICI discontinuation rates caused by toxicities ranged from 0% to 23.5%. Original data were extracted from six studies, covering 89 patients. Patients in whom 1L-ICIs were discontinued following clinical decision (the mPFS of 2L-ICIs was not reach) achieved a more prolonged mPFS of 2L-ICIs than those due to toxicity (5.2 months) and progressive disease (2.1 months) (p < 0.0001). Patients' 1L-PFS for more than 2-years had preferable 2L-ORR (35.0% vs. 9.8%, p = 0.03), 2L-DCR (85.0% vs. 49.0%, p = 0.007), and 2L-mPFS (12.4 vs. 3.0 months, p < 0.0001) than those less than 1-year. Patients administered the same drugs achieved a significantly prolonged mPFS compared with the remaining patients (5.4 vs. 2.3 months, p = 0.0004), and those who did not accept antitumor treatments during the intervals of two lines of ICIs achieved a prolonged mPFS compared to those patients who did accept treatments (7.6 vs. 1.9 months, p < 0.0001).

Conclusions: ICI rechallenge is a useful therapeutic strategy for NSCLC patients, especially suitable for those who achieve long-term tumor remission for more than 2-years under 1L-ICIs.

Keywords: immune checkpoint inhibitor; meta-analysis; non-small cell lung cancer; predictive factor; rechallenge.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung*
  • Databases, Factual
  • Humans
  • Immune Checkpoint Inhibitors
  • Lung Neoplasms*
  • Progression-Free Survival

Substances

  • Immune Checkpoint Inhibitors