Tachihara Motoko, Shoda Hiroyasu, Akazawa Yuki, Ota Takayo, Oki Masahide, Sato Yuki, Sugawara Shunichi, Ikeda Satoshi, Yokoyama Toshihide, Kaneda Hiroyasu, Itoh Shoichi, Bessho Akihiro, Katakami Nobuyuki, Morita Satoshi, Nakagawa Kazuhiko, Okamoto Isamu, Yamamoto Nobuyuki
Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Department of Respiratory Medicine, Hiroshima Citizens Hospital, Japan.
Lung Cancer. 2025 Aug;206:108637. doi: 10.1016/j.lungcan.2025.108637. Epub 2025 Jun 29.
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/m, days 1,8,15 and cisplatin 60 mg/m, 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.
程序性死亡受体1配体（PD-L1）抑制剂联合依托泊苷-铂类（EP）是广泛期小细胞肺癌（ES-SCLC）的标准一线治疗方案。然而，它们的疗效仍不尽人意。伊立替康-顺铂（IP）是ES-SCLC的可选方案，且伊立替康已显示出潜在的免疫刺激活性。本研究评估了IP联合度伐利尤单抗治疗初治ES-SCLC的疗效和安全性。
符合条件的患者（年龄20-74岁；体力状况评分0-1）接受四个周期的IP方案（伊立替康60mg/m²，第1、8、15天；顺铂60mg/m²，第1天）联合度伐利尤单抗1500mg，随后每4周给予度伐利尤单抗1500mg。主要终点是12个月无进展生存期（PFS）率，由独立中央审查（ICR）评估。
2021年5月至2022年11月期间，共纳入42例患者（中位年龄66岁；76.2%为男性；31.0%体力状况评分为0）。ICR评估的12个月PFS率为18.8%（90%CI，9.3-30.8%），中位PFS为5.7个月（95%CI，4.9-7.6个月）。中位总生存期（OS）为16.9个月（95%CI，11.8-未达到），12个月OS率为65.8%（95%CI，49.1-78.1）。确认的总缓解率（ORR）为65.9%，疾病控制率（DCR）为85.4%。≥3级不良事件（AE）发生率为73.8%，包括2例5级事件（2.4%；肺炎和肝炎）。肺炎发生率为4.8%（1级和5级），3级及以上腹泻发生率为7.1%。
REBORN研究未证明IP联合度伐利尤单抗在初治ES-SCLC中具有预期疗效，其疗效和安全性总体上与EP联合度伐利尤单抗相当。
