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    Liver and Lung Metastases Impact Progression-Free and Overall Survival in Rare Cancers

    Wang et alJournal of immunotherapy and precision oncology

    Liver and Lung Metastases Impact Progression-Free and Overall Survival in Rare Cancers
    An analysis of the SWOG S1609 basket trial (NCT02834013, DART trial) evaluated whether liver and/or lung metastases were associated with clinical outcomes among 655 eligible patients with advanced rare tumors, excluding lung or liver primary cancers, treated with combination anti-CTLA-4 and anti-PD-1 therapy. Outcomes assessed included clinical benefit rate (defined as confirmed complete or partial response or stable disease for 6 months or longer), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events.
    Safety analyses revealed no significant difference in rates of grade 3 or higher treatment-related adverse events across the metastatic groups. In contrast, efficacy endpoints differed by metastatic site: patients with both liver and lung metastases had an 11% clinical benefit rate and those with liver but not lung metastases had an 18% rate, compared with 26% in patients with lung but not liver metastases and 30% in those with neither metastatic site (p = 0.003).
    In multivariable Cox regression models adjusting for the number of RECIST target sites, the concurrent presence of both lung and liver metastases was associated with shorter PFS and OS compared with the presence of neither site. When compared to the absence of both sites, isolated lung metastases or isolated liver metastases were significantly associated with PFS, but not with OS.

    Key Takeaways

    • Clinical benefit rates with combination anti-CTLA-4 and anti-PD-1 therapy were 11% for patients with both liver and lung metastases and 18% for liver metastases alone, compared with 26% for lung metastases alone and 30% for neither metastatic site (p = 0.003).
    • On multivariable analysis accounting for RECIST target site counts, concurrent lung and liver metastases were associated with shorter PFS and OS compared to neither site, whereas isolated lung or liver metastases were significantly associated with PFS but not OS.
    • Rates of grade 3 or higher treatment-related adverse events showed no significant difference across metastatic site groups.
    Read the original sourceJournal of immunotherapy and precision oncology