Retreatment with immune checkpoint inhibitors in solid tumors: a systematic review

Abstract

Background: A large proportion of patients eventually experience disease progression despite treatment with immune checkpoint inhibitors (ICIs), but subsequent treatment options are limited for this population. Retreatment with the same or different types of ICIs is a possible strategy, but the clinical efficacy and safety data are limited. This systematic review aims to evaluate the efficacy and safety of ICIs retreatment in patients with solid tumors after disease progression to previous ICIs. Methods: We searched MEDLINE, EMBASE, the Cochrane Library, and major meeting libraries for prospective studies. The primary outcomes included the objective response rate (ORR), disease control rate (DCR), median overall survival (mOS), and the incidence of grade ⩾3 immune-related adverse events (irAEs). Results: We identified 22 prospective studies including 1865 patients. For disease progression after CTLA-4 inhibitors, three studies evaluated anti-CTLA-4 retreatment. The ORR was 12–23%, the DCR was 48.4–67.7%, and the mOS was 12 months. The incidence of grade ⩾3 irAEs was 5.9–25%. Four studies evaluated anti-programmed cell death protein 1 (PD-1) retreatment. The ORR was 22–36%, the DCR was 40–64%, and the mOS was 13.4–20.6 months. The incidence of grade ⩾3 irAEs was <10%. For disease progression after PD-(L)1 inhibitors, 13 studies evaluated anti-PD-(L)1 retreatment. The ORR was 5–53%, the DCR was 38–83%, and the mOS was 13.9 months. The incidence of grade ⩾3 irAEs was 0–15% for patients retreated with single anti-PD-(L)1 agent, but was higher (0–64%) for those retreated with ICIs combined with other agents. Two studies evaluated anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) retreatment. The ORR was 0–22.4%, the DCR was 50–72%, and the mOS was 4–21 months. The incidence of grade ⩾3 irAEs was 26–61%. Conclusion: Retreatment with ICIs is feasible for cancer patients considering its encouraging efficacy and tolerable safety. Further prospective trials are needed to explore more promising strategies and identify suitable populations for retreatment.