Sequential chemo-durvalumab, reduced dose RT, and consolidation durvalumab for unresectable stage III NSCLC unfit for PACIFIC regimen (DEDALUS trial)

INTRODUCTION: The PACIFIC study established the standard of care for unresectable, stage III non-small cell lung cancer. The DEDALUS trial is a Phase 2, open-label, multicenter study enrolling patients who are eligible for sequential CRT plus immunotherapy. METHODS: Patients had unresectable stage IIIA-C NSCLC, regardless of PD-L1 status. After three cycles of chemo-durvalumab, responders received hypofractionated thoracic radiotherapy (45 Gy over three weeks) with durvalumab, then continued durvalumab for up to 12 months or until disease progression. Primary endpoint was safety, assessed by the incidence of Grade 3 and 4 possibly related adverse events (PRAEs) within six months. Secondary endpoints included PFS, OS and quality of life (NCT05128630). RESULTS: Between February 2022 and August 2024, 28 patients were screened, and 25 enrolled across three Italian centers. Enrollment was halted early due to low recruitment. We recorded 9 Grade 3 to 4 PRAEs, which accounted for 6.4% of all AEs; 7 patients (28%) experienced at least one grade 3 to 4 PRAE. Only one was immune-related, while the remaining PRAEs were related to chemotherapy, none to RT.Median PFS was 13.2 months (95% CI: 4.9-18.6), median OS was 17.5 months (95% CI: 10.7-18.6). Among the 16 patients who started maintenance without progression median PFS was 18.6 months (95% CI: 12.8-not reached), median OS was not reached. CONCLUSIONS: The early closure of the study and the reduced sample size make it difficult to draw significant conclusions. However, feasibility and safety seem to be acceptable, early PFS and OS data are promising, especially for patients who completed the full treatment sequence.