Thoracic radiotherapy plus maintenance durvalumab after first line carboplatin and etoposide plus durvalumab in extensive-stage disease small cell lung cancer (ES-SCLC) - A multicenter single arm open label phase II trial (SAKK 15/19).

Background Small cell lung cancer (SCLC) is an aggressive tumour type accounting for 10-15 % of lung cancers. The role of thoracic radiotherapy (TRT) in extensive stage SCLC (ESSCLC) in the era of checkpoint inhibitors (CPIs) is undefined. Methods SAKK 15-19 is a national, multicenter, single-arm prospective phase II study evaluating consolidative TRT after standard first-line chemotherapy plus durvalumab in ES-SCLC. Patients (pts) with confirmed ES-SCLC and ECOG ≤ 1 received carboplatin AUC5 (day 1), etoposide 100 mg/m² (days 1-3) and durvalumab 1500 mg (day 1) for 4 cycles, followed by maintenance durvalumab every 4 weeks for up to 2 years in pts without progression. TRT (39 Gy in 13 fractions over 2. 5 weeks) was delivered within 5 weeks after chemoimmunotherapy. Prophylactic cranial irradiation was permitted. The primary endpoint was 12-month progression-free rate (PFR) ; secondary endpoints included progression-free survival (PFS), response rate and overall survival (OS). The study aimed at a 12-month PFR ≥ 25 % (H1) vs. ≤ 12. 5 %. Results Forty-six pts were enrolled; 37 % had ECOG 0, 30 % had asymptomatic brain metastases. At 29-month follow-up, the 12-month PFR was 15. 6 (95 % CI 7-27. 5), median PFS 6. 4 months (95 % CI 4. 8-7. 2) and median OS 15. 0 months (95 % CI 10. 2-22. 0). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 23. 9 % of pts, mainly neutropenia (23. 9 %) and thrombocytopenia (8. 4 %). One pt (2 %) had grade 5 sepsis; no severe TRT-related toxicities were observed. Conclusions Adding consolidative TRT after chemotherapy plus durvalumab in ES-SCLC didn't meet the primary endpoint of the expected 12-month PFR. No additional severe toxicities from TRT were observed. Ongoing larger Phase III trials, including RAPTOR (LNRG LU007), will further define TRT's role in this setting.