Researchers from Japan recently reported that the first phase II study to evaluate the efficacy and safety of durvalumab and concurrent curative radiation therapy for PD-L1–positive unresectable locally advanced non–small cell lung cancer (NSCLC) without chemotherapy met its primary endpoint with tolerable adverse reactions. The research was reported at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (Abstract MA06.04).
Immunotherapy plays an important role in NSCLC, and the combination of radiotherapy and immunotherapy have been reported to have a synergistic effect. Durvalumab after concurrent chemoradiotherapy has been the standard of care with unresectable locally advanced NSCLC (stage III/postoperative recurrent NSCLC). But some patients are unable to complete concurrent curative radiation therapy and cannot receive durvalumab.
Study Details
Motoko Tachihara, MD, PhD, of Kobe University Graduate School of Medicine, Japan, and colleagues developed the DOLPHIN study—the first phase II study of immunotherapy combined with curative radiotherapy for unresectable locally advanced NSCLC.
Dr. Tachihara and researchers at 12 research locations in Japan enrolled 35 adults with unresectable locally advanced NSCLC who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, PD-L1 ≥ 1% (SP263 clone). Patients received curative radiation therapy (60 Gy) plus durvalumab at 10 mg/kg every 2 weeks simultaneously, followed by maintenance with durvalumab for up to 12 months until disease progression or unacceptable toxicity.
Between September 2019 and November 2020, 35 patients were enrolled from 12 institutions in Japan. The median participant age was 72 years. Of the 35 patients, 88.6% were male, 54.3% had an ECOG performance status of 0, 96.1% had a history of smoking, 57.1% had nonsquamous histology, and 25.7% experienced postoperative recurrence
Key Findings
A total of 34 patients were evaluated for safety, and 33 patients for efficacy. The 12-month progression-free survival rate as assessed by independent central review was 72.1% (90% confidence interval [CI] = 59.1–85.1) after a median follow-up of 18.7 months. The confirmed overall response rate was 90.9% (95% CI = 75.7–98.1) with complete and partial response rates of 36.4% and 54.5%, respectively. Median progression-free survival was not reached according to independent central review and 24.1 months (95% CI = 16.0 months to not reached) by investigator assessment.
A total of 13 patients (39.4%) discontinued durvalumab—6 patients due to disease progression and 7 due to adverse events. Grade 3 to 4 adverse events occurred in 47.1%; the most common grade 3 to 4 adverse events were lung infection (11.8%) and pneumonitis (11.8%). Grade 5 adverse events of any cause occurred in two patients (5.9%), one with lung infection and one with bronchoesophageal fistula because of tumor progression during follow-up.
