Outcomes of Patients with Rare Cancers Treated with Immune Checkpoint Inhibitors with and Without Lung and/or Liver Metastases (NCI/SWOG S1609).
6 affiliations
- 1Department of Statistics, University of California Davis, Davis, CA, USA.
- 2SWOG Cancer Research Network Statistical Center, Seattle, WA, USA.
- 3Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
- 4Department of Medicine, Hematology and Oncology, Northwestern University, Chicago, IL, USA.
- 5Department of Medical Oncology, University of California at San Diego Moores Cancer Center, La Jolla, CA, USA.
- 6Department of Medical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
Abstract
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. 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. 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. 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.
Related
- 971 The impact of liver metastases on immune-related adverse events in stage IV patients treated with immune-checkpoint inhibitors: a real-world, multicenter, retrospective study
- Association of pre-existing cardiovascular disease with cardiovascular and clinical outcomes in patients receiving immune checkpoint inhibitors
- Successful Treatment of Synchronous Double Lung and Colon Cancers Using Immune Checkpoint Inhibitors
- Distinct changes in plasma protein profiles of cancer patients receiving immune checkpoint inhibitors versus chemotherapy: implications for thrombosis risk and adverse outcomes
- Association between antibiotic exposure and survival outcomes in hepatocellular carcinoma patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis
BibTeX
@article{wang2026outcomes,
title = {{Outcomes of Patients with Rare Cancers Treated with Immune Checkpoint Inhibitors with and Without Lung and/or Liver Metastases (NCI/SWOG S1609).}},
author = {Yichen Wang and Megan Othus and Young Kwang Chae and Madison Davies and Eliana Dietrich and Sandip P Patel and Razelle Kurzrock},
journal = {Journal of immunotherapy and precision oncology},
year = {2026},
month = nov,
doi = {10.36401/jipo-26-29},
url = {https://europepmc.org/article/MED/42999803},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Outcomes of Patients with Rare Cancers Treated with Immune Checkpoint Inhibitors with and Without Lung and/or Liver Metastases (NCI/SWOG S1609).
AU - Yichen Wang
AU - Megan Othus
AU - Young Kwang Chae
AU - Madison Davies
AU - Eliana Dietrich
AU - Sandip P Patel
AU - Razelle Kurzrock
PY - 2026
DA - 2026/11/06
JO - Journal of immunotherapy and precision oncology
DO - 10.36401/jipo-26-29
UR - https://europepmc.org/article/MED/42999803
AB - 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. 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. 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. 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.
SN - 2666-2345
SN - 2590-017X
ER -