Tislelizumab plus sitravatinib or anlotinib as maintenance therapy in extensive-stage small-cell lung cancer: Results of two prospective phase II studies.

First-line chemo-immunotherapy has significantly improved survival in extensive-stage small-cell lung cancer (ES-SCLC). However, rapid disease progression still occurs, with a median progression-free survival (PFS) of only 4.5-5.8 months from induction therapy. We initiated two single-arm, phase II studies to assess the first-line maintenance therapy with tislelizumab plus anti-angiogenic drugs following induction therapy in ES-SCLC patients. Previously untreated ES-SCLC patients were enrolled to receive tislelizumab plus platinum-based chemotherapy as induction therapy for 4 cycles, followed by tislelizumab plus sitravatinib (Trial 1) or anlotinib (Trial 2) as maintenance therapy in a 21-day cycle. The primary endpoint was the 1-year PFS rate in the maintenance analysis set (MAS, including patients receiving ≥1 dose of maintenance therapy). Outcomes in MAS were calculated from the start of maintenance therapy. Twenty-one patients were enrolled, and 18 patients entered the maintenance phase in each trial. From the start of the maintenance therapy, the median PFS was 6.4 and 7.8 months (1-year PFS rates of 22.2% and not reached), respectively; the median overall survival (OS) was 18.3 months and not reached. From induction therapy, the corresponding median PFS was 9.1 and 10.8 months, with a median OS of 17.6 months and not reached. In MAS, the most common grade ≥3 treatment-related adverse events (TRAEs) included hypertension (22.2%) in Trial 1 and fatigue (5.6%) in Trial 2. No patients died from TRAEs in either trial. Maintenance therapy with tislelizumab plus sitravatinib or anlotinib yielded clinically meaningful survival results and was generally well tolerated in ES-SCLC, warranting further exploration in larger-scale trials.