Outcomes of Patients with Rare Cancers Treated with Immune Checkpoint Inhibitors with and Without Lung and/or Liver Metastases (NCI/SWOG S1609)

ABSTRACT Introduction 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-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and anti-PD-1 (programmed cell death protein 1) 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 survival (PFS) and overall survival (OS) were evaluated with Cox regression models. Associations with clinical benefit rate (confirmed complete and partial response or stable disease for 6 months or longer) and treatment-related adverse events (per CTCAEv5) were evaluated using Fisher 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 with 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, having both lung and liver metastases was associated with shorter PFS and OS compared with the presence of neither liver nor lung metastases when accounting for the number of RECIST (Response Evaluation Criteria in Solid Tumors) target sites. Compared with the presence of neither liver nor lung metastases, lung but not liver or liver but not lung sites of metastases were significantly associated with PFS but not OS in these multivariable models. 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 the combination of lung and liver metastases was associated with shorter PFS and OS.