First-Line Durvalumab Plus Irinotecan and Cisplatin Showed Potential for Patients With Extensive-Stage Small Cell Lung Cancer

According to results from the phase 2 REBORN trial, first-line durvalumab plus irinotecan and cisplatin demonstrated efficacy and safety among patients with extensive-stage small cell lung cancer (ES-SCLC). 

“PD-L1 inhibitors combined etoposide-platinum are standard first-line treatments for [ES-SCLC] … however, their efficacy remains suboptimal,” stated Motoko Tachihara, MD, PhD, Kobe University Graduate School of Medicine, Kobe, Japan, and coauthors. “Irinotecan-cisplatin is optional regimen for ES-SCLC, and irinotecan has shown potential immunostimulatory activity.” 

In this prospective, single-arm study, 42 chemotherapy-naive patients received 60 mg/m² of irinotecan (on days 1, 8, and 15) and 60 mg/m² of cisplatin (on day 1) with 1500 mg of durvalumab followed by maintenance durvalumab every 4 weeks in 4 cycles until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). Key secondary end points included overall survival (OS), overall response rate (ORR), disease control rate, duration of response, and safety. 

At a median follow-up of 14.5 months, median PFS was 5.7 months and the 12-month PFS rate was 18.8%. Median OS was 16.9 months, and the 12-month OS rate was 65.8%. The confirmed ORR was 65.9% and the disease control rate was 85.4%. Median duration of response was 5.6 months. Grade ≥3 adverse events occurred in 73.8% of patients. The most common grade 3/4 events included leukopenia, neutropenia, anemia, diarrhea, nausea, and diarrhea. Grade 5 pneumonitis was reported in 1 patient. Grade ≥3 durvalumab-related adverse events occurred in 17 patients. 

“This treatment strategy did not show the expected efficacy, but its efficacy and safety were generally comparable to conventional etoposide-based chemoimmunotherapy,” concluded Dr Tachihara et al. “Strategies to extend the durable efficacy of antitumor immunity to more patients by administering targeted therapies to those most likely to respond are urgently needed and are currently being actively explored.”

Source: 

Tachihara M, Shoda H, Akazawa Y, et al. Durvalumab plus irinotecan + cisplatin for untreated extensive-stage small cell lung cancer: REBORN, phase II study (WJOG13520L). Lung Cancer. Published online: June 29, 2025. doi: 10.1016/j.lungcan.2025.108637