Background: Currently, patients with unresectable stage III non-small-cell lung cancer (NSCLC) ineligible for chemotherapy receive radiotherapy alone, with unsatisfactory results. DUART was a phase II single-arm trial of durvalumab in patients without progression after radiotherapy for unresectable stage III NSCLC. Patients and methods: Patients were enrolled into parallel cohorts per radiotherapy dose (A: definitive; B: palliative) and received durvalumab (1500 mg every 4 weeks for up to 12 months). The primary endpoint was incidence of grade 3/4 possibly related adverse events (PRAEs) within 6 months of durvalumab initiation. Secondary endpoints included objective response rate, progression-free survival (PFS), and overall survival (OS). Exploratory circulating tumor (ctDNA) analyses utilized a targeted methylation assay (GRAIL, Inc.). Results: As of 06 December 2023, 102 patients received durvalumab (cohort A: 53; cohort B: 49); 18.8%/73.3%/7.9% had Eastern Cooperative Oncology Group performance status 0/1/2 and median age was 79.0 years. Overall, 9.8% [95% confidence interval (CI) 4.8% to 17.3%] had grade 3/4 PRAEs within 6 months of durvalumab initiation. Median PFS (investigator assessed) was 9.2 months, with a 12-month landmark rate of 39.6%. Median OS was 21.1 months and the 12-month landmark rate was 64.7%. Patients who were ctDNA positive at cycle 1 or 7 had shorter PFS versus patients who were ctDNA negative at the same time point. Conclusions: The safety profile of durvalumab after radiotherapy was consistent with PACIFIC (durvalumab after chemoradiotherapy). Efficacy across cohorts was encouraging. Some patients may achieve or maintain molecular remission with durvalumab even after palliative radiotherapy. Durvalumab following radiotherapy may be a potential treatment option in a frailer, older, chemotherapy-ineligible population.
Filippi, A., García Campelo, M., Paoli, J., Kowalski, D., Bennati, C., Borghetti, P., et al. (2025). Durvalumab after radiotherapy in patients with unresectable stage III non-small-cell lung cancer ineligible for chemotherapy: the DUART phase II nonrandomized controlled study. ESMO OPEN, 10(9) [10.1016/j.esmoop.2025.105560].
Durvalumab after radiotherapy in patients with unresectable stage III non-small-cell lung cancer ineligible for chemotherapy: the DUART phase II nonrandomized controlled study
Cortinovis, D.;
2025
Abstract
Background: Currently, patients with unresectable stage III non-small-cell lung cancer (NSCLC) ineligible for chemotherapy receive radiotherapy alone, with unsatisfactory results. DUART was a phase II single-arm trial of durvalumab in patients without progression after radiotherapy for unresectable stage III NSCLC. Patients and methods: Patients were enrolled into parallel cohorts per radiotherapy dose (A: definitive; B: palliative) and received durvalumab (1500 mg every 4 weeks for up to 12 months). The primary endpoint was incidence of grade 3/4 possibly related adverse events (PRAEs) within 6 months of durvalumab initiation. Secondary endpoints included objective response rate, progression-free survival (PFS), and overall survival (OS). Exploratory circulating tumor (ctDNA) analyses utilized a targeted methylation assay (GRAIL, Inc.). Results: As of 06 December 2023, 102 patients received durvalumab (cohort A: 53; cohort B: 49); 18.8%/73.3%/7.9% had Eastern Cooperative Oncology Group performance status 0/1/2 and median age was 79.0 years. Overall, 9.8% [95% confidence interval (CI) 4.8% to 17.3%] had grade 3/4 PRAEs within 6 months of durvalumab initiation. Median PFS (investigator assessed) was 9.2 months, with a 12-month landmark rate of 39.6%. Median OS was 21.1 months and the 12-month landmark rate was 64.7%. Patients who were ctDNA positive at cycle 1 or 7 had shorter PFS versus patients who were ctDNA negative at the same time point. Conclusions: The safety profile of durvalumab after radiotherapy was consistent with PACIFIC (durvalumab after chemoradiotherapy). Efficacy across cohorts was encouraging. Some patients may achieve or maintain molecular remission with durvalumab even after palliative radiotherapy. Durvalumab following radiotherapy may be a potential treatment option in a frailer, older, chemotherapy-ineligible population.
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