信迪利单抗联合多西他赛二线治疗无驱动基因变异的晚期非小细胞肺癌的 II 期疗效和生物标志物研究。

Sintilimab plus docetaxel as second-line therapy of advanced non-small cell lung cancer without targetable mutations: a phase II efficacy and biomarker study.

机构信息

Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China.

Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.

出版信息

BMC Cancer. 2022 Sep 5;22(1):952. doi: 10.1186/s12885-022-10045-0.

BACKGROUND

Single-agent immunotherapy is currently the recommended second-line therapy for patients with advanced non-small cell lung cancer (NSCLC) without targetable mutations; however, the objective response rate (ORR) remains low. This phase II study evaluated the efficacy of the combination therapy of sintilimab plus docetaxel and explored potential biomarkers for efficacy prediction.

METHODS

Thirty patients with NSCLC without targetable mutations whose disease progressed from first-line platinum-based chemotherapy from October 2019 to December 2020 were enrolled in this single-arm, single-center, phase II trial. Sintilimab (200 mg) and docetaxel (75 mg/m) were administered every 3 weeks until progression. The primary endpoint was ORR. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Biomarker analyses of blood and tissue samples were also performed.

RESULTS

Among 30 patients, 11 patients had partial response, resulting in an ORR of 36.7%. The median PFS was 5.0 months (95%CI: 3.9-6.1) and OS was 13.4 months (95%CI: 5.6-21.2). The most common immune-related adverse event of any grade was hepatitis, observed in 23.3% (7/30) of patients. Treatment-emergent adverse events were manageable. Patients detected with high PD-L1 expression in circulating tumor cells (cutoff value ≥32.5% based on the median CTC-PD-L1 expression) achieved significantly higher ORR (60% versus 13.3%, p = 0.021) and significantly longer median PFS (6.0 versus 3.5 months, p = 0.011) and median OS (15.8 versus 9.0 months, p = 0.038) than those with low CTC-PD-L1 level. Patients detected with PD-L1 < 1% and CD8 ≥ 1% expression from their baseline tissue samples had significantly higher ORR (83.3% versus 12.5%, p = 0.026) but similar PFS (p = 0.62) and OS (p = 0.15).

CONCLUSION

This study demonstrated the effectiveness and safety of sintilimab plus docetaxel as a second-line treatment of NSCLC without targetable mutations after progression from first-line platinum-based chemotherapy.

TRIAL REGISTRATION

This study was registered in the Clinical trials registry with ClinicalTrials.gov Identifier NCT03798743 (SUCCESS).

背景

对于无靶向突变的晚期非小细胞肺癌（NSCLC）患者，单药免疫治疗目前是推荐的二线治疗方法；然而，客观缓解率（ORR）仍然较低。这项 II 期研究评估了信迪利单抗联合多西他赛联合治疗的疗效，并探讨了预测疗效的潜在生物标志物。

方法

2019 年 10 月至 2020 年 12 月，30 例无靶向突变且一线含铂化疗后进展的 NSCLC 患者入组本单臂、单中心、II 期研究。每 3 周给予信迪利单抗（200mg）和多西他赛（75mg/m），直至进展。主要终点为 ORR。次要终点包括无进展生存期（PFS）、总生存期（OS）和安全性。还对血液和组织样本进行了生物标志物分析。

结果

30 例患者中，11 例患者部分缓解，ORR 为 36.7%。中位 PFS 为 5.0 个月（95%CI：3.9-6.1），OS 为 13.4 个月（95%CI：5.6-21.2）。任何级别的最常见免疫相关不良事件是肝炎，见于 23.3%（7/30）的患者。治疗相关不良事件可管理。在循环肿瘤细胞（CTC-PD-L1 表达中位数为截断值≥32.5%）中检测到高 PD-L1 表达的患者，其 ORR 显著更高（60%与 13.3%，p=0.021），中位 PFS （6.0 与 3.5 个月，p=0.011）和中位 OS（15.8 与 9.0 个月，p=0.038）显著更长。基线组织样本中 PD-L1<1%和 CD8≥1%表达的患者，ORR 显著更高（83.3%与 12.5%，p=0.026），但 PFS（p=0.62）和 OS（p=0.15）相似。