Durvalumab-containing treatment for recurrent or metastatic pulmonary sarcomatoid carcinoma: A pooled post hoc analysis of two KCSG phase II trials

Introduction: Pulmonary sarcomatoid carcinoma (PSC) is a rare cancer characterized by a high programmed death-ligand 1 (PD-L1) expression, suggesting a potential therapeutic benefit from immune checkpoint inhibitors. We investigated the efficacy of durvalumab-containing combination therapy and explored potential predictive biomarkers in patients with recurrent or metastatic (R/M) PSC. Method: In this pooled post hoc analysis, data were integrated from two prospective phase II trials (NCT03022500 and NCT04224337) wherein durvalumab-containing combination therapies were evaluated in patients with R/M PSC. PD-L1 expression was assessed using 22C3 or SP263 assays, and circulating lymphocyte subsets were analyzed using flow cytometry. Results: Overall, 33 patients were included, of whom 66.7 % had a PD-L1 tumor proportion score (TPS) ≥ 1 % and 45.5 % had a TPS ≥ 50 %. The overall response rate was 33.3 % (95 % confidence interval [CI], 18.0 %–51.8 %), and the disease control rate was 72.7 % (95 % CI, 54.5 %–86.7 %). The median progression-free survival and overall survival were 5.4 (95 % CI, 2.8–9.4) and 15.7 (95 % CI, 11.3–not estimated) months, respectively. PD-L1 expression was not associated with the response or survival outcomes. Patients who achieved disease control exhibited a higher proportion of circulating CD8⁺ T cells (mean, 28.5 % vs. 20.3 %, P = 0.083) and a lower CD4⁺/CD8⁺ ratio (median, 1.4 vs. 1.7, P = 0.048) than did those with progressive disease. Conclusion: Durvalumab-containing combination therapy showed promising efficacy in patients with R/M PSC, irrespective of PD-L1 expression. A lower CD4⁺/CD8⁺ ratio may be associated with favorable disease control.