Durvalumab plus irinotecan + cisplatin for untreated extensive-stage small cell lung cancer: REBORN, phase II study...

PD-L1 inhibitors combined etoposide-platinum (EP) are standard first-line treatments for extensive-stage small-cell lung cancer (ES-SCLC). However, their efficacy remains suboptimal. Irinotecan-cisplatin (IP) is optional regimen for ES-SCLC, and irinotecan has shown potential immunostimulatory activity. This study evaluated the efficacy and safety of IP plus durvalumab in untreated ES-SCLC.

Eligible patients (aged 20-74 years; PS 0-1 received four cycles of IP (irinotecan 60 mg/m², days 1,8,15 and cisplatin 60 mg/m², day 1) with durvalumab 1500 mg, followed by durvalumab 1500 mg every 4 weeks. Primary endpoint was the 12-month progression-free survival (PFS) rate, assessed by an independent central review (ICR).

Between May 2021 and Nov 2022, 42 patients (median age, 66 years; 76.2 % were male; 31.0 % had PS 0) were enrolled. The 12-month PFS rate by ICR was 18.8 % (90 % CI, 9.3-30.8 %), with a median PFS of 5.7 months (95 % CI, 4.9-7.6 months). Median overall survival (OS) was 16.9 months (95 % CI, 11.8-NE), and the 12-month OS rate was 65.8 % (95 % CI, 49.1-78.1). Confirmed overall response rate (ORR) was 65.9 %, and disease control rate (DCR) was 85.4 %. Grade ≥3 adverse events (AEs) occurred in 73.8 %, including two grade 5 (2.4 %; pneumonitis and hepatitis). Pneumonitis occurred in 4.8 % (grade 1 and 5), while diarrhea of grade 3 or more occurred in 7.1 % patients.

The REBORN study did not demonstrate the expected efficacy of IP plus durvalumab in untreated ES-SCLC, with its efficacy and safety generally comparable to those of EP plus durvalumab.