Durvalumab impacts progression-free survival while high-dose radiation >66 Gy improves local control without excess toxicity in unresectable NSCLC stage III: Real-world data from the Austrian radio-oncological lung cancer study association registry (ALLSTAR)

Background Chemo-radioimmunotherapy with total radiation doses of 60–66 Gy in 2 Gy fractions is the standard of care for non-small cell lung cancer (NSCLC) UICC stage III. The Austrian radio-oncological lung cancer study association registry (ALLSTAR) is a prospective multicentre registry intended to document clinical practice at the beginning of the Durvalumab era. Patients and methods Patients were eligible if they had pathologically verified unresectable NSCLC stage III with a curative treatment option. Chemo-radiation combined with immunotherapy was performed according to local treatment practices. The endpoints were local control (LC), progression-free survival (PFS) and toxicity. Results Between 2020/03 and 2023/04, 12/14 (86 %) Austrian radiation-oncology centres recruited 188 patients (median 17, range: 1–89). PD-L1 testing was performed in 173/188 (93 %) patients. The median interval between the end of chemoradiotherapy and start of Durvalumab was 14 days (range: 1–65). About 40 % (75/188) of the patients received a total radiation dose of > 66 Gy (range: 67.1–100), which improved 2-year LC (86 % versus 60 %, HR = 0.41; 95 %-CI: 0.17–0.98; log-rank p-value < 0.05). Median PFS for patients with Durvalumab was 25.8 months (95 %-CI: 21.9-not reached) compared to 15.7 months (95 %-CI: 13.2–27.8) for those without (HR = 1.88; 95 %-CI: 1.16–3.05; log-rank p-value < 0.01). The rates of esophageal and pulmonary toxicities were 34.6 % and 23.9 %, respectively, including one case of grade 4 pneumonitis. In the subcohort of 75 patients who received > 66 Gy, 19 (25 %) cases of pulmonary toxicity grades 1–3 were observed. Conclusion While Durvalumab impacts PFS, LC can be improved by total radiation doses > 66 Gy without excess toxicity.