KEY POINTS
- ALLSTAR is a nationwide prospective Austrian registry involving 12 of 14 radiation oncology centres. This final analysis included 228 patients with unresectable stage III NSCLC, of whom 156 received Durvalumab after CRT and 72 received CRT alone.
- Median follow-up was approximately 41 months with Durvalumab and 38 months without. Most patients received IMRT/VMAT, although both concurrent and sequential CRT were permitted and dose-fractionation was heterogeneous.
- Durvalumab was associated with longer PFS: median 22.8 versus 16.5 months, with 3-year PFS of 43% versus 27% and HR 0.61 (p=0.0071).
- Median overall survival was 52.6 months with Durvalumab versus 27.4 months without, with 3-year OS of 60% versus 46% and HR 0.52 (p<0.002).
- Distant and local composite outcomes also favored immunotherapy. Median time to death or distant metastasis was 33.3 versus 18.7 months, while time to death or local relapse was 30.4 versus 17.2 months.
- After multivariable adjustment, Durvalumab remained independently associated with PFS, OS, distant-metastasis-related outcome and local-relapse-related outcome. ECOG performance status was another major independent prognostic factor.
- The exploratory radiation question is more controversial. Patients receiving both >66 Gy EQD2 and Durvalumab had median intrathoracic control of 37.0 months versus 17.7 months among patients receiving neither, with 3-year rates of 53% versus 34%. The association narrowly missed statistical significance (HR 0.61; p=0.051).
- Pneumonitis occurred more frequently with Durvalumab (34% vs 21%; p=0.050). Three pneumonitis-related deaths occurred overall; two were in Durvalumab-treated patients, both of whom had received >66 Gy EQD2, underscoring the uncertainty around combining substantial dose escalation with immunotherapy.
- The dose-escalation signal is highly confounded. Durvalumab-treated patients had smaller primary GTVs and higher delivered tumor doses, treatment was not randomized, high doses were more common at high-volume centres, and immortal-time and imaging-review biases cannot be fully excluded.
CLINICAL TAKEAWAY
ALLSTAR provides mature real-world confirmation that Durvalumab after CRT remains associated with substantially better long-term outcomes in stage III NSCLC. The suggestion that RT escalation beyond 66 Gy may further improve intrathoracic control is hypothesis-generating only and should not overturn current dose standards, particularly given the pneumonitis concern.