Treatment-related adverse events and response rate to immune checkpoint inhibition

BACKGROUND: Immune checkpoint inhibition (ICI) represents a novel treatment modality for refractory cancers, and improving prediction of potential responders is critical. METHOD: We hypothesized that ICI is a systemic-effecting mechanism. The objective response rate (ORR) for anti-PD-1, anti-PD-L1, anti-CTLA-4, or combination therapy was plotted against the corresponding all-grade and grade 3–4 (G3/4) treatment-related adverse events (TRAEs) across several cancer types using an extensive literature search (MEDLINE and Google Scholar; December 1, 2012–December 30, 2017). RESULTS: Sixty-six eligible studies comprised 76 cohorts and 25 cancer types. A significant correlation was present between all-grade or G3/4 TRAEs and the ORR. The correlation coefficient was 0.5 for all-grade and 0.4 for G3/4 TRAEs, suggesting that >50% of the differences in the ORR across cancer types may be reflected by TRAEs and 40% of ORR differences may be predicted by G3/4 TRAEs. Hodgkin’s lymphoma and Merkel cell carcinoma showed a better response, while adrenocortical cancer, breast cancer, and uveal melanoma showed a worse response, compared with that predicted by TRAE. CONCLUSION: There is a strong relationship between TRAEs and ICI activity across multiple cancers. The toxicity profile compared with the ORR to ICIs should be investigated in phase I trials.