Durvalumab联合依托泊苷和卡铂用于广泛期小细胞肺癌伴间质性肺疾病的多中心开放性前瞻性试验

Durvalumab with etoposide and carboplatin for patients with extensive-stage small cell lung cancer and interstitial lung disease: A multicenter, open-label prospective trial

LUNG CANCER

影响因子:4.4

分区:医学2区 / 肿瘤学3区呼吸系统3区

发表日期:2024 Oct

作者: Ryota Shibaki, Daichi Fujimoto, Eisaku Miyauchi, Yoko Tsukita, Ichiro Nakachi, Daisuke Arai, Yoshihiko Sakata, Naoki Shingu, Toshio Shimokawa, Takashi Kijima, Motohiro Tamiya, Sachiko Kawana, Satoshi Hara, Go Saito, Yuki Sato, Toshihide Yokoyama, Shinya Sakata, Yoshihiko Taniguchi, Akito Hata, Hirotaka Matsumoto, Teppei Yamaguchi, Nobuyuki Yamamoto

DOI: 10.1016/j.lungcan.2024.107958

摘要

部分指南建议在伴有既存间质性肺疾病（ILD）患者中谨慎使用免疫治疗，因为抗癌治疗引起肺炎的发生率较高。为评估化疗免疫治疗在伴有轻度特发性间质性肺炎（IIP）的小细胞肺癌（SCLC）患者中的安全性，有必要开展前瞻性临床试验。本研究评估了广泛期（ES）SCLC伴轻度特发性间质性肺炎患者接受化疗免疫治疗的安全性和疗效。在本多中心前瞻性试验中，招募了伴有轻度慢性纤维性IIP的ES-SCLC患者。轻度IIP定义为排除肺功能不良、明确的肺泡间质性肺炎（UIP）型以及血清自抗体阳性。患者每三周接受一次durvalumab、依托泊苷和卡铂（诱导期），随后每四周接受1500 mg durvalumab（维持期）。主要终点为严重肺炎无病率。共分析21名患者，其中13名表现出可能的UIP型，8名表现为不确定UIP型。在诱导期中，2例（9.5%）发生任何级别的肺炎，一例为1级肺炎，一例为5级肺炎。维持期未发生其他肺炎病例。严重肺炎无病率为95.2%（95%置信区间（CI）：77.3%-99.2%）。中位无进展生存期（PFS）为5.5个月（95% CI：3.6-6.4个月），中位总生存期（OS）为10.7个月（95% CI：6.0个月，尚未达到）。化疗免疫联合治疗是伴有轻度IIP的ES-SCLC患者的可行治疗方案。

Abstract

Certain guidelines recommend caution when administering immunotherapy in patients with pre-existing interstitial lung disease (ILD) owing to the high incidence of pneumonitis induced by anti-cancer therapy. A prospective clinical trial assessing the safety of chemoimmunotherapy in patients with small-cell lung cancer (SCLC) and pre-existing ILD is warranted. Therefore, this study evaluated the safety and efficacy of chemoimmunotherapy in patients with extensive-stage (ES)-SCLC and mild idiopathic interstitial pneumonia (IIP).In this multicenter prospective trial, patients with ES-SCLC and pre-existing mild chronic fibrosing IIP were recruited. Mild IIP was defined as the exclusion of poor pulmonary function, a definite usual interstitial pneumonia (UIP) pattern, and positivity for autoantibodies in blood tests. The patients received durvalumab, etoposide, and carboplatin every three weeks (induction phase), followed by 1,500 mg durvalumab every four weeks (maintenance phase). The primary endpoint was severe pneumonitis-free rate.Twenty-one patients were included in the analysis. Among them, 13 patients displayed a probable UIP pattern, whereas eight patients exhibited an indeterminate for UIP pattern. Two patients (9.5 %) had pneumonitis of any grade during the induction phase; one had Grade 1 and the other had Grade 5 pneumonitis. No other patient developed pneumonitis during the maintenance phase. The severe pneumonitis-free rate was 95.2 % (95 % confidence interval (CI): 77.3-99.2 %). The median progression-free survival was 5.5 months (95 % CI: 3.6-6.4 months). Median overall survival was 10.7 months (95 % CI: 6.0 months to not reached).Chemoimmunotherapy is a feasible treatment approach for patients with ES-SCLC and mild IIP.