The first phase II study to assess the safety and efficacy of durvalumab and concurrent curative radiation therapy for PD-L1-positive locally advanced non-small cell lung cancer without chemotherapy met its primary endpoint with manageable adverse events, according to researchers from Japan. The study was presented today in Vienna, Austria, during the IASLC 2022 World Conference on Lung Cancer.
In NSCLC, immunotherapy is crucial, and studies have shown that radiation and immunotherapy together have synergistic effects. Standard of care for unresectable locally advanced non-small cell lung cancer (stage III/postoperative recurrent NSCLC) has been durvalumab given along with chemoradiotherapy. However, some individuals cannot receive durvalumab and cannot complete concomitant curative radiation therapy.
The DOLPHIN study was created by Dr. M. Tachihara from Kobe University Graduate School of Medicine in Kobe, Japan, and colleagues. It is the first Phase II study of immunotherapy paired with curative radiation for locally advanced non-small cell lung cancer that cannot be surgically removed.
35 adult patients with unresectable locally advanced non-small cell lung cancer and an ECOG performance status (PS) 0-1, PD-L11 percent were enrolled by Dr. Tachihara and researchers at 12 study facilities in Japan (SP263 clone). Patients underwent concurrent curative radiation therapy (60Gy) and maintenance with durvalumab (10 mg/kg) every two weeks, up to a maximum of 12 months, until disease progression (PD) or intolerable toxicity.
A total of 35 patients from 12 Japanese institutions were enrolled between September 2019 and November 2020. Of the 35 patients, 88.6% were male, 54.3 % had ECOG PS 0, 96.1 % had smoked before, 57.1 % had non-squamous histology, and 25.7 % had postoperative recurrence. The median age of the patients was 72 years.
34 patients underwent safety evaluations, while 33 individuals underwent efficacy evaluations. After a median follow-up of 18.7 months, the 12-month progression-free survival rate by ICR was 72.1% (90 percent CI, 59.1-85.1). With complete and partial response rates of 36.4 percent and 54.5 percent, respectively, the confirmed overall response rate was 90.9 percent (95 percent CI, 75.7-98.1, ICR-assessed). ICR-assessed median progression-free survival was not achieved, while investigator-assessed median progression-free survival was 24.1 months (95 percent CI, 16.0-NR). Thirteen patients (39.4%) stopped using durvalumab; six due to disease progression and seven due to side effects (AE). 47.1 percent of adverse events were grade 3 or grade 4; lung infection (11.8 percent) and pneumonitis were the most prevalent grade 3/4 adverse events (11.8 percent ). Due to tumour progression during follow-up, grade 5 adverse events of any cause occurred in 2 patients (5.9%), one with a lung infection and the other with a broncho-esophageal fistula.
“The combination of immunotherapy and curative radiation for unresectable LA-NSCLC is reported for the first time in this DOLPHIN research. The 12-month PFS rate’s primary endpoint was reached and was significantly higher than anticipated. It implies that this treatment approach is effective, has manageable side effects, and is suitable as a study treatment for phase III trials “Dr. Tachihara added.