Checkpoint inhibitors linked to longer unadjusted progression-free survival in advanced thoracic tumors

A cohort study of 98 patients at Shanghai Chest Hospital found that immune checkpoint inhibitor-containing therapy was associated with longer unadjusted progression-free survival than chemotherapy without checkpoint inhibitors in advanced SMARCA4-deficient thoracic tumors. The comparison included 16 patients in each treatment group. Median progression-free survival was 8.6 months with checkpoint inhibitor-containing therapy and 4.5 months with chemotherapy alone, with a hazard ratio of 0.36, a 95% confidence interval of 0.15–0.85 and P = 0.020.

Neither progression-free survival nor overall survival remained statistically significant after adjustment for clinical covariates and stratification by pathological group, making the treatment findings hypothesis-generating rather than confirmatory. The study included patients diagnosed between May 2019 and September 2023. Investigators analyzed clinical features across the full cohort, disease-free survival and overall survival among patients who underwent complete surgical resection, and progression-free survival and overall survival in advanced, non-resectable disease.

These rare and highly aggressive tumors are typically associated with mutations or deletions of the SMARCA4 gene. Within the resection cohort, researchers recorded 22 disease-free survival events and 13 deaths. Pathological stage and tumor group were independently associated with disease-free survival.

Relative to stage III, stage I–II disease was associated with a lower risk of a disease-free survival event, with a hazard ratio of 0.23, a 95% confidence interval of 0.08–0.63 and P = 0.004. Stage and preoperative neutrophil-to-lymphocyte ratio, or NLR, were associated with overall survival. Stage I–II disease carried a lower mortality risk than stage III, with a hazard ratio of 0.11, a 95% confidence interval of 0.02–0.53 and P = 0.006, while NLR above 3.92 was associated with a higher risk, with a hazard ratio of 4.20, a 95% confidence interval of 1.19–14.80 and P = 0.025.

These analyses identify factors associated with outcomes but do not establish that stage or NLR causes the differences. In the advanced-stage comparison, objective response rates were 50.0% among the 16 patients receiving checkpoint inhibitor-containing therapy and 12.5% among the 16 receiving chemotherapy without checkpoint inhibitors; the difference had P = 0.054. The unadjusted overall-survival comparison favored checkpoint inhibitor-containing therapy numerically: median overall survival had not been reached in that group, compared with 15.3 months in the chemotherapy-only group.

The hazard ratio was 0.41, but the 95% confidence interval was 0.13–1.27 and P was 0.122, indicating that the unadjusted overall-survival association was not statistically significant. After covariate adjustment and stratification by pathological group, neither progression-free survival nor overall survival retained statistical significance. The small treatment groups and imprecise adjusted estimates limit conclusions about whether checkpoint inhibitors confer an outcome benefit independent of other patient and disease characteristics.

The researchers also assessed potential response markers in 19 unique patients treated with checkpoint inhibitors. PD-L1 expression was not statistically associated with either progression-free survival or overall survival. The NLR cutoff and CDKN2A findings were described as exploratory and requiring independent validation.

Overall, the study associates postoperative stage and pathological group with disease-free survival, and stage and preoperative NLR with overall survival. In advanced disease, checkpoint inhibitor-containing therapy was associated with longer unadjusted progression-free survival, but the adjusted results were not statistically significant.

Subject of Research: Clinical outcomes and checkpoint inhibitor treatment in advanced SMARCA4-deficient thoracic tumors

Article Title: Clinical outcomes of SMARCA4-deficient thoracic tumor patients and therapeutic value of immune checkpoint inhibitors in advanced stage patients

Article References: Jiang, Q., Mu, S., Sun, Y., & Yu, Y. (2026). Clinical outcomes of SMARCA4-deficient thoracic tumor patients and therapeutic value of immune checkpoint inhibitors in advanced stage patients. BMC Cancer. https://doi.org/10.1186/s12885-026-16850-1

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16850-1

Keywords: SMARCA4, thoracic tumors, immune checkpoint inhibitors, progression-free survival, overall survival, non-small cell lung cancer, neutrophil-to-lymphocyte ratio, PD-L1, CDKN2A, clinical outcomes, Clinical, outcomes