Heterogeneity in advanced pulmonary sarcomatoid carcinoma and its efficacy to immune checkpoint inhibitors

Highlights•The efficacy of ICIs in PSC was poorly explored.•The mPFS for PSC receiving ICIs was 8.77 m (95 % CI, 4.21-13.32).•The addition of anti-angiogenic therapy with ICIs increased PFS of PSC.•The median TMB of PSC was 6.3 mutations per million base pairs.AbstractBackgroundImmune checkpoint inhibitors (ICIs) have improved the prognosis of patients with non-small cell lung cancer but rarely been explored in pulmonary sarcomatoid carcinoma (PSC). This multicenter study aimed to evaluate the effectiveness of ICIs for PSC and its underlying mechanism.MethodsAdvanced PSC who received ICIs between August 2018 and May 2022 from 11 centers in China were included. Clinical characteristics and treatment information were collected. Whole-exome sequencing (WES) and whole transcriptome sequencing were conducted on pre-treatment samples to explore the mechanism.Results113 patients with PSC were enrolled, the median PFS for patients receiving ICIs therapy was 8.77 months (95 % confidence interval, 4.21 to 13.32). Combining ICIs with anti-angiogenic agents significantly increased PFS (p = 0.04). Liver metastasis and combination therapy with anti-angiogenic agents were independent risk factors for PFS (Hazard Ratio [HR] = 3.652, p = 0.019 and HR = 0.435, p = 0.017, respectively). WES showed that PSC presented with a TMB of 6.3 mutations per million base pairs. High expression of TNFα signaling and glycolysis related gene showed a better prognosis.ConclusionsICIs showed promising benefits for advanced PSC, and the addition of anti-angiogenic therapy might be a more effective treatment strategy for this disease.