Durvalumab plus platinum-etoposide in extensive-stage extrapulmonary small cell carcinoma (ES-EPSCC): Second safety assessment of the DURVASCC trial (GOIRC-01-2021).

Abstract

e14572 Background: EPSCC is a rare and highly aggressive malignancy with a poor prognosis. The low incidence has limited prospective evidence for first-line (1L) treatment. Given histological similarities with small cell lung cancer, where immunotherapy plus chemotherapy (CT) is the standard of care, an agnostic strategy was adopted. The DURVASCC trial aims to evaluate the clinical activity and safety of durvalumab plus platinum–etoposide as 1L treatment in ES-EPSCC. Methods: DURVASCC is an Italian, multicenter, phase II, single-arm study. Patients received durvalumab 1500 mg with carboplatin AUC5-6 or cisplatin 75-80 mg/m 2 on day1 plus etoposide 80-100 mg/m 2 day1-3 Q2W for 4-6 cycles, followed by durvalumab 1500 mg Q4W in patients achieving disease control until progression or unacceptable toxicity, for a max of 24 months. Safety assessment was pre-specified using a continuous toxicity monitoring design based on a Pocock-type group sequential approach, with planned evaluations every 10 patients up to 30 enrolled, each with a minimum follow-up of one month. Early stopping rules were based on the cumulative number of clinically relevant adverse events (AEs). At the second assessment, trial discontinuation would have been triggered if ≥6 relevant AEs (defined as events leading to treatment interruption or withdrawal) had been observed. Safety data and stopping rules were periodically reviewed by an independent data and safety monitoring board. Results: As of November 2025, 20 patients were evaluable for safety. Fifteen patients (75%) experienced at least one AE considered possibly related to durvalumab, with or without concomitant attribution to CT. Seven Grade 4 AEs occurred in five patients; three were serious, and one (thrombocytopenia) led to temporary treatment interruption. Eight Grade 3 AEs occurred in four patients: one (pan-uveitis) was unresolved and resulted in permanent treatment discontinuation.According to the primary safety definition, two AEs were classified as relevant, corresponding to a rate of 10% (95% confidence interval [CI]: 1.2%–31.7%).In a sensitivity analysis including additional Grade 3–4 events more likely attributable to concomitant CT, three patients experienced relevant AEs (two neutropenia—one unresolved and one leading to treatment delay—and one serious febrile neutropenia), corresponding to a rate of 25% (95% CI: 8.7%–49.1%). In both analyses, the pre-specified early stopping threshold of six relevant AEs was not exceeded. Conclusions: Based on the second safety assessment, durvalumab plus platinum–etoposide showed a manageable safety profile, supporting continuation of the DURVASCC trial. Clinical trial information: NCT06464068 .