Rechallenge of immune checkpoint inhibitors: A systematic review and meta-analysis

Abstract

Background: The role of immune checkpoint inhibitors (ICI) rechallenge in cancer patients is not defined. When ICIs are discontinued due to treatment completion or toxicity, another course of ICIs is feasible in clinical practice, but the amount of data is still quite limited to draw definitive conclusions. Here we report the results of a meta-analysis evaluating efficacy and safety of ICI rechallenge.

Methods: PubMed, Embase, and Cochrane library were searched for studies reporting efficacy and safety of ICI rechallenge. Pooled analysis of response rate (ORR), median progression-free survival (mPFS) and median overall survival (mOS) were calculated.

Results: A total of 49 studies were included in qualitative and quantitative pooled analysis Overall response rate, mPFS and mOS were 21.8 % (range 0-70 %), 4.9 months (range 0-19.1 months) and 15.6 months (range 5.1-39 months), respectively. Incidence of any grade and grade 3-4 adverse events were 52.2 % (range 4-100 %) and 21.5 % (range 0-97.8 %), respectively. In the subgroup of patients who had previously discontinued ICI because of disease progression ORR, mPFS and mOS were 15.2 %, 2.9 and 7.9 months. Patients who had previously discontinued ICI because of toxicity achieved an ORR of 44 % and a mPFS of 13.2 months with the rechallenge.

Conclusions: Our results suggest that rechallenge ICI is an active and feasible strategy, and it could be considered on an individual basis. However, this analysis is based on non-randomized studies. Prospective studies are needed to clarify the role of rechallenge after disease progression or adverse events.

Keywords: Immune checkpoint inhibitors; Meta-analysis; Outcome; Rechallenge; Solid tumors.