Outcomes of patients with rare cancers treated with combination immune checkpoint inhibitors with and without lung and/or liver metastases (NCI/SWOG S1609).

2633 Background: Limited prior retrospective data, primarily among patients with lung cancer, liver cancer, and melanoma, has indicated that liver metastases are associated with poorer outcomes with chemotherapy, targeted agents, and checkpoint inhibitor therapy. We used a unique clinical trial resource to evaluate whether liver and/or lung metastases were associated with outcomes among patients with rare tumors treated with combination anti-PD-1 and anti-CTLA-4 therapy. Methods: The basket trial, SWOG trial S1609 (NCT02834013, DART trial), treated 655 eligible patients without lung or liver primary cancers. Associations with progression-free and overall survival were evaluated with Cox regression models; multivariable models controlled for age at trial registration, sex, performance status, race, ethnicity, primary tumor organ. Associations with clinical benefit rate (confirmed complete and partial response or stable disease for six months or longer) and treatment-related adverse events were evaluated using Fisher’s exact test. Results: There was no significant difference in rates of grade 3 or higher treatment-related adverse events across the groups. Participants with liver metastases, with or without lung metastases, had a lower likelihood of experiencing clinical benefit (11% and 18%, respectively) compared to participants with lung but not liver metastases or participants with neither lung nor liver metastases (26% and 30%, respectively, p=0.003). On multivariable analysis, both lung and liver metastases were associated with shorter progression-free and overall survival compared to presence of neither liver nor lung metastases. Conclusions: In a diverse cohort of participants with advanced rare tumors treated with combination anti-CTLA-4 and anti-PD-1 therapy, we found that both lung and liver metastases were associated with shorter progression-free and overall survival. Multivariable Cox regression models for progression-free survival and overall survival. Covariate Progression-free survival Overall survival Lung but not liver metastases (N=175) (reference = neither liver nor lung, N=269) 1.40(1.13-1.72) 0.0019 1.24(1.00-1.55)0.053 Liver but not lung metastases N=154) (reference = neither liver nor lung, N=269) 1.73(1.38-2.17) <0.001 1.33(1.05-1.68) 0.017 Liver and lung metastases N=57) (reference = neither liver nor lung, N=269) 1.96(1.44-2.65) <0.001 1.91(1.40-2.61) <0.001 Liver but not lung metastases N=154) (reference = lung but not liver, N=175) 1.24(0.96-1.60)0.095 1.07(0.83-1.38)0.62 Liver and lung metastases N=57) (reference = lung but not liver, N=175) 1.40(1.02-1.92) 0.037 1.54(1.11-2.12) 0.009 Liver and lung metastases N=57) (reference = liver but not lung, N=154) 1.13(0.83-1.55)0.45 1.44(1.04-1.99) 0.030 Hazard ratio (95% confidence interval) p-value reported.