A phase II study of durvalumab (MEDI4736) immediately after completion of chemoradiotherapy in unresectable stage III non–small cell lung cancer: TORG1937 (DATE study).

Abstract

8536 Background: Concurrent chemoradiotherapy followed by durvalumab maintenance for up to 12 months is the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). However, the best timing of starting durvalumab after completion of chemoradiation has not been identified. Progression-free survival (PFS) and overall survival (OS) were better in the subgroup of patients administered durvalumab within 14 days after last radiation to randomization according to the PACIFIC study (Antonia SJ, et al. 2017, 2018 NEJM). Methods: This study was a prospective, single-arm, multicenter, phase II clinical trial. Eligibility criteria included patients with unresectable stage III NSCLC, ECOG PS 0-1, age < 75 years old. Patients who did not have disease progression after definitive concurrent chemoradiotherapy (CCRT) (chemotherapy: 2 cycles of platinum-based doublet chemotherapy, radiotherapy: 60 Gy/30 Fr) received durvalumab (10 mg/kg, every 2 weeks for up to 12 months) from the next day (allowed up to 5 days) after last radiation. The primary endpoint was 1-year PFS rate from registration assessed by an independent review committee. The planned sample size was 47 with a threshold value of 50% based on results of the PACIFIC study, an expected value of 63%, one-sided alpha of 20% and power of 80% in 1-year PFS rate. Results: From January 2020 to August 2020, 50 patients were enrolled from 16 institutions and 47 patients were evaluable for efficacy and safety. Forty-two patients received durvalumab maintenance therapy. Patient characteristics were: male/female 41/6; median age 65 (range 42-75); ECOG PS 0/1 28/19; IIIA/IIIB/IIIC 19/21/7. The 1-year PFS rate from registration was 75.0% (60% CI: 69.0 to 80.0). The 1-year OS rate from registration was 97.7% (95%CI: 84.6 to 99.7). ORR, median PFS and median OS were 78.7%, 14.2 months (95%CI: 13.4 to not reached (NR)) and NR, respectively. Grade 3/4 adverse events were pneumonitis (4.3%), neutropenia (44.7%), febrile neutropenia (4.3%). There was no treatment-related death. Conclusions: Our study met the primary endpoint. Durvalumab can be safely administered immediately after completion of CCRT for patients with unresectable stage III NSCLC, no additional or unexpected toxicity occurred as a reference to the PACIFIC study. Clinical trial information: jRCTs031190117.