Retreatment, rechallenge, and escalation with subsequent immune checkpoint inhibitor therapies across cancers after...

Immune checkpoint inhibitors (ICIs) are used across many tumor types in perioperative and advanced settings. However, most patients discontinue treatment due to disease progression, adverse events, or other reasons. Clinical benefit of using ICIs following discontinuation is not well defined.

We analyzed the literature examining ICI treatment outcomes after progression or discontinuation in different tumor types. We extracted data from 51 studies, assessed the strength of the evidence, summarized treatment options, and identified gaps in our understanding.

We proposed definitions for the different scenarios of subsequent treatment with ICIs. In melanoma, studies frequently reported complete response (CR), partial response (PR), and stable disease (SD) following subsequent ICI therapy. In renal cell carcinoma, discordant results have been reported following subsequent ICI treatment; some trials reported CR/PR cases, whereas others did not show any CR/PR. In non-small-cell lung cancer, we found frequent reports of PR or SD but not CR following subsequent ICI treatment, although studies had small patient cohorts. Subsequent ICI treatment showed efficacy in some patients with urothelial carcinoma, but the small cohort sizes limited the strength of the evidence. One cross-tumor study investigated subsequent ICI treatment after initial discontinuation and reported a few PR and SD without any CR.

Evidence supporting the efficacy of subsequent ICI treatment is strongest in melanoma, but the level of evidence remains low overall. Prospective studies and improved reporting of subsequent ICI therapy in existing trials investigating long-term outcomes, standardized predictive factors, and treatment modalities are warranted.