Sintilimab plus chemotherapy for first-line treatment of advanced pulmonary lymphoepithelioma-like carcinoma: Phase 2 trial.

Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a unique non-small cell lung cancer associated with Epstein-Barr virus (EBV), lacking a standard treatment. This phase 2 study evaluates sintilimab plus gemcitabine and carboplatin (4 cycles), followed by sintilimab maintenance in 30 untreated patients with locally advanced or metastatic PLELC. At a median follow-up of 42.4 months, the objective response rate is 73.3% and disease control is 100.0%. The median progression-free survival (PFS) is 13.5 months (95% confidence interval [CI], 12.2-24.5), and median overall survival is 46.9 months (95% CI, 29.5-not reached [NR]). Grade ≥3 treatment-related adverse events occurred in 70.0% of patients, mainly neutropenia (46.7%). Higher T cell-inflamed gene-expression profile score is associated with longer PFS (p = 0.003). Plasma EBV-DNA levels decrease with treatment response and increase with disease progression. Sintilimab plus chemotherapy shows promising efficacy with manageable safety as first-line treatment for advanced PLELC. This study was registered at ClinicalTrials.gov (NCT04312204).