Durvalumab plus anlotinib versus durvalumab alone as maintenance treatment in extensive-stage small-cell lung cancer (DURABLE): a multicenter, randomized, phase II trial and biomarker analysis.

Although first-line immunotherapy plus chemotherapy has made substantial progress in extensive-stage small-cell lung cancer (ES-SCLC), the survival benefit remains limited. DURABLE was a prospective, multicenter, open-label, randomized, phase II trial (NCT04985851) that evaluated the efficacy and safety of durvalumab plus anlotinib as consolidative maintenance therapy following first-line durvalumab plus platinum-etoposide chemotherapy in ES-SCLC. The primary endpoint was blinded independent central review-assessed progression-free survival (PFS) from randomization, with a two-sided p-value of <0.20 considered statistically significant. 66 patients were randomly assigned to maintenance therapy with durvalumab plus anlotinib (n = 34) or durvalumab alone (n = 32). Durvalumab plus anlotinib significantly improved PFS compared with durvalumab alone, with median PFS from randomization of 5.4 months versus 1.9 months (HR = 0.64; 80% CI, 0.44-0.94; p = 0.12). The incidence of grade 3-4 treatment-related adverse events in the combination and monotherapy groups was 24.2% and 12.5%, respectively. Patients with impaired antigen presenting capacity or low bTMB tended to show improved outcomes with combined maintenance therapy. While similar efficacy between the two groups was observed in patients with high antigen presenting capacity or high bTMB. These findings suggest that durvalumab plus anlotinib might be an effective and well-tolerated maintenance treatment option in ES-SCLC.