Treatment-related adverse events as surrogate to response rate to immune checkpoint blockade

BACKGROUND: Immune checkpoint blockade (ICB) brings hope to many late-stage cancer patients yet its marker for response remains elusive. METHODS: We developed a hypothesis that treatment-related adverse events (TrAEs) could predict objective response rate (ORR) to ICB. We plotted ORR against corresponding any and grade 3 to 5 (G3–5) TrAEs across a variety of cancer types by performing a meta-analysis using linear regression. RESULTS: We identified 113 eligible studies encompassing 25 types of malignancies that were treated with ICB or ICB-based regimes. A significant linear correlation was observed for any and severe TrAEs, respectively. The correlation coefficient was 0.57 (r(2) = 0.324) for any TrAE and 0.61 (r(2) = 0.37) for G3–5 TrAE. For melanoma, the correlation coefficient was 0.81 (r(2) = 0.57) for any TrAE and 0.65 (r(2) = 0.42) for G3–5 TrAEs. For RCC, the correlation coefficient was 0.86 (r(2) = 0.74) for any TrAE and 0.91 (r(2) = 0.83) for G3–5 TrAE. For NSCLC, the correlation coefficient was 0.55 (r(2) = 0.3) for any TrAE and 0.74 (r(2) = 0.86) for G3–5 TrAE. For UC, the correlation coefficient was 0.47 (r(2) = 0.68) for any TrAE and 0.27 (r(2) = 0.52) for G3–5 TrAE, yet the correlation was insignificant for severe AEs. CONCLUSION: Our findings suggest that over half of ICB responses could be reflected by any adverse events and ∼60% of responses could be reflected by severe AEs. Further validation is needed in individual trials.