BACKGROUND

Associations between immune-related adverse events from checkpoint inhibitor therapy and outcomes have been previously evaluated, with most prior research finding a positive association between toxicity and survival. This prior research has generally reported on more common tumor types. We use a unique data resource of a federally funded basket trial (NCT02834013) for patients with rare cancers (n = 684) to evaluate associations between immune-related adverse events and overall survival and progression-free survival (PFS).

METHODS

Patients were treated with nivolumab and ipilimumab; the trial was opened at more than 1000 sites. Landmark Cox regression models were used to assess first cycle immune-related adverse event associations with PFS and overall survival.

RESULTS

We found that grade 1-2 treatment-related immune-related adverse events in the first cycle of therapy were associated with longer overall survival (multivariable hazard ratio [HR] = 0.61, 95% confidence interval [CI] = 0.49 to 0.75; P < .001) compared with no treatment-related immune-related adverse event, while grade 3-4 immune-related adverse events were associated with shorter overall survival (HR = 1.41, 95% CI = 1.04 to 1.90; P = .025). Similar but weaker associations were observed with PFS and grade 1-2 treatment-related immune-related adverse events (HR = 0.83, 95% CI = 0.67 to 1.01; P = .067) and grade 3-4 (HR = 1.35, 95% CI = 1.02 to 1.78; P = .037) compared with no treatment-related immune-related adverse events. Grade 1-2 dermatologic toxicity was associated with improved overall survival compared with other grade 1-2 toxicities (HR = 0.67, 95% CI = 0.52 to 0.85; P = .002). There was no statistically significant overall survival difference between patients with grade 1-2 fatigue, gastrointestinal, metabolic, hepatic, endocrine, and thyroid toxicities vs other grade 1-2 toxicities.

CONCLUSION

In this large cohort of patients with rare tumors receiving checkpoint inhibitor therapy, grade of immune-related adverse event in the first cycle was predictive for survival.