LBA62 Durvalumab after radiotherapy (RT) in patients with unresectable stage III NSCLC ineligible for chemotherapy (CT): Primary results from the DUART study

Consolidation durvalumab following chemoradiotherapy (CRT) is SOC for patients (pts) with unresectable Stage III NSCLC. Many pts, however, are ineligible for CT and mainly receive RT alone with unsatisfactory results. We report the primary safety and secondary efficacy analyses of DUART (NCT04249362), a phase 2, open-label international study. Pts with unresectable Stage III NSCLC deemed ineligible for CT by a multidisciplinary team with no progression after RT were enrolled into two parallel cohorts per prior RT dose according to local SOC (A: standard RT, 60 Gy ± 10% or bioequivalent dose [BED]; B: palliative RT, 40 to <54 Gy or BED). Pts received durvalumab 1500 mg IV Q4W for 12 mo or until progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was safety/tolerability, defined by the incidence of grade 3/4 possibly-related adverse events (PRAEs) occurring within 6 mo of the first dose. 102 pts received durvalumab. Median total treatment (Tx) duration was 30.6 wk; Tx is ongoing in 21 pts. Median age was 79.0 yr; 71.6% were male, and 18.8%/73.3%/7.9% had ECOG performance status (PS) 0/1/2. Overall, 9.8% (A: 11.9%; B: 7.0%) had grade 3/4 PRAEs within 6 mo of the first dose (primary endpoint). Median PFS was 8.0 mo and confirmed ORR was 26.5%. The most common PRAE leading to discontinuation was pneumonitis, in 3.9% of pts. 7 pts (A: 5; B: 2) had fatal AEs, including 1 PRAE (A: pneumonitis). Key clinical outcomes are summarized in the table. Additional results, including overall survival, will be presented.Table: LBA62Cohort A (standard RT; n=59)Cohort B (palliative RT; n=43)Total (N=102)Any PRAEs, %a Gr 3/4 Gr 3/4 (within 6 mo)67.8 15.3 11.948.8 7.0 7.059.8 11.8 9.8PFS Events (%) Median (95% CI), mob 12-mo PFS rate (95% CI), %b26 (44.1) 9.0 (5.6–NC) 40.2 (23.6–56.3)25 (58.1) 7.6 (5.3–11.0) 29.3 (13.8–46.7)51 (50.0) 8.0 (7.0–9.7) 34.8 (23.0–46.9)Confirmed ORR (95% CI),c %28.8 (17.8–42.1)23.3 (11.8–38.6)26.5 (18.2–36.1)Data cutoff: Mar 30, 2023 (median [range] follow-up, 7.4 mo [0.0–24.9] in all censored pts). aInvestigator-assessed.bEstimated by Kaplan–Meier method. cCIs calculated by Clopper-Pearson exact method.NC, not calculable; ORR, objective response rate; PFS, progression-free survival. Open table in a new tab Data cutoff: Mar 30, 2023 (median [range] follow-up, 7.4 mo [0.0–24.9] in all censored pts). aInvestigator-assessed. bEstimated by Kaplan–Meier method. cCIs calculated by Clopper-Pearson exact method. NC, not calculable; ORR, objective response rate; PFS, progression-free survival. We demonstrate in a prospective trial that pts ineligible for CT, including pts with PS 2, can be safely treated with a combination of thoracic RT followed by immunotherapy. Preliminary efficacy outcomes were encouraging (numerically better in the 60 Gy cohort), making this combination a novel option for this common subset of more fragile pts.