Durvalumab Plus High-Dose Radiation in NSCLC III: Long-Term Results from the Austrian Radio-Oncological Lung Cancer Study Association Registry (ALLSTAR).

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.