Abstract / Summary
Purpose: Chemoradioimmunotherapy (CRIT) with 60–66 Gy is the standard of care (SoC) for non-small-cell lung cancer (NSCLC) UICC stage III. The aim of this real-world data (RWD) study was to report the long-term impact of Durvalumab and radiation dose escalation on clinical outcomes. Material and Methods: ALLSTAR is a nationwide prospective multicentre registry for NSCLC UICC stage III, in which 12/14 Austrian centres participated (ethics approval number: 1002/2019). The basis for the current analysis is the third data extraction, which was completed on 2 June 2025. Apart from the SoC, alternative dose-fractionation and sequential CRT concepts >66 Gy were also permitted. Durvalumab maintenance treatment for one year was administered at the discretion of the tumour board at each centre. Results: Compared to prior analyses by our group, 40 individuals who completed follow-up (FUP) were added to this final analysis, leading to a total patient population of 228 (156 CRT plus Durvalumab; 72 CRT). In 156 patients, Durvalumab was added to CRT, while 72 received CRT only. The median FUP periods were 41.0 (95%-CI: 36.7–45.4) and 37.8 months (95%-CI: 31.4–44.1) for the Durvalumab and CRT cohort, respectively. Radiation dose escalation combined with Durvalumab treatment was associated with a nominally higher ITC of 37 months (95%-CI: 24.5-not reached) compared with 17.7 months (95%-CI: 14.9-not reached) in patients receiving neither dose escalation nor Durvalumab (N = 135; HR = 0.61; 95%-CI: 0.37–1.006; p-value 0.051). With Durvalumab maintenance, a median PFS of 22.8 months (95%-CI: 19.4–38.3) was observed compared to 16.5 months (95%-CI: 12.6–24.5) without (N = 228; HR = 0.61; 95%-CI: 0.42–0.88; p-value 0.0071). Median OS was 52.6 months (95%-CI: 39.5-not reached) with Durvalumab compared to 27.4 months (95%-CI: 18.7-not reached) without (N = 228; HR = 0.52; 95%-CI: 0.34–0.78; log-rank p-value < 0.002). Median time to death or distant metastasis (TTDM) was 33.3 months (95%-CI: 23.5–45) in the Durvalumab cohort compared to 18.7 months (95%-CI: 14.8-not reached) in the CRT cohort (N = 228; HR = 0.60; 95%-CI: 0.42–0.89; log-rank p-value 0.01). Median time to death or local relapse (TDLR) with Durvalumab was 30.4 months (95%-CI: 23.5–51.1) compared to 17.2 months (95%-CI: 14.8–25.7) without (N = 226; HR = 0.58; 95%-CI: 0.40–0.83; log-rank p-value < 0.003). Conclusion: This final RWD analysis implies both a beneficial effect of high-dose irradiation combined with Durvalumab on ITC and the long-lasting impact of Durvalumab on PFS, OS, TTDM, and TDLR.