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.