First-Line Platinum-Based Chemotherapy with Novel Systemic Agents for Unresectable or Metastatic Thymic Epithelial...

Thymic epithelial tumors, including thymomas and thymic carcinomas (TC), are rare thoracic malignancies with poor prognosis in advanced stages. Platinum-based chemotherapy (CT) remains the first-line standard with limited efficacy. Novel systemic therapies, such as immune checkpoint inhibitors (ICIs) and antiangiogenic agents, have exhibited promise in refractory disease.

A systematic search of PubMed, EMBASE, and Cochrane was performed for studies including patients with unresectable, recurrent, or metastatic thymic epithelial tumors treated with platinum-based CT combined with ICIs or antiangiogenic agents. Meta-analyses were conducted using a random-effects model, with heterogeneity assessed through the I ² statistic and Cochran's Q test.

Nine studies encompassing 208 patients were included, of which 93.7% had TC. The data set comprised five phase II trials and four retrospective cohorts. The pooled 12-month overall survival rate was 96.08% (95% confidence interval [CI]: 84.80-99.08), and 12-month progression-free survival was 56.68% (95% CI: 45.82-70.44). The median duration of response and median progression-free survival were 11.96 (95% CI: 6.32-22.64) months and 16.22 (95% CI: 10.30-25.52) months, respectively, with a pooled objective response rate of 57.69% (95% CI: 43.99-70.3). The objective response rate was 68.50% for antiangiogenic and 51.19% for ICIs combinations. Any-grade treatment-related adverse events occurred in 88.65%, grade 3 or higher in 30.22%, and grade 3 or higher immune-related adverse events in 11.62%, with treatment discontinuation in 13.55%.

Platinum-based CT combined with ICIs or antiangiogenic agents exhibits promising efficacy and manageable toxicity, particularly in TC. Evidence in thymomas remains limited, and severe immune-related toxicity warrants caution. Randomized trials are needed for confirmation.