First-line toripalimab in combination with platinum-doublet chemotherapy for advanced B3 thymoma and thymic carcinoma: an open-label prospective phase Ⅱ trial

Background Several studies have demonstrated the efficacy of programmed cell death protein 1/programmed death-ligand 1 (PD-L1) inhibitors in patients with thymic epithelial tumors (TETs). Previous trials suggest that the efficacy of immunotherapy in TETs is associated with specific features of the tumor immune microenvironment. Patients and methods Patients received a combination of paclitaxel, carboplatin, and toripalimab every 3 weeks for up to six cycles, followed by toripalimab maintenance every 4 weeks until disease progression or other discontinuation criteria. The primary endpoint was progression-free survival (PFS). Immunohistochemistry and next-generation sequencing were used to assess the association between various biomarkers and efficacy. Results Between November 2020 and January 2024, 24 patients were enrolled in the study. The median PFS was 19.3 months [95% confidence interval (CI) 12.8-25.8]. The objective response rate was 37.5% (95% CI 18.8%-59.4%) and the disease control rate was 100% (95% CI 85.8%-100%). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 12 (50.0%) patients. Common grade 3-4 TRAEs included decreased neutrophil, white blood cell, and platelet counts. Immune-related adverse events (irAEs) were identified in 11 (45.8%) patients; grade ≥3 irAEs were reported in 1 (4.2%) patient. Patients with higher PD-L1 expression showed a trend toward longer PFS. Further analysis revealed a specific infiltration pattern of CD8+ T cells, M1/M2 macrophages, and CD56 bright natural killer cells in the tumor immune microenvironment and mutations in the nuclear factor κB pathway were associated with better clinical outcomes. Conclusions Toripalimab combined with carboplatin and paclitaxel is an emerging therapeutic option for patients with thymic carcinoma and B3 thymoma. The overall incidence and severity of adverse events are within the acceptable range. Tumor microenvironment features or mutational signatures are credible prognostic indicators.