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

作者：Yongchang Zhang, Lianxi Song, Liang Zeng, Yi Xiong, Li Liu, Chunhua Zhou, Haiyan Yang, Zhan Wang, Qing Xia, Wenjuan Jiang, Qinqin Xu, Nong Yang · 发表于：BMC Cancer · 年份：2022 · DOI：10.1186/s12885-022-10045-0 · 被引用次数：20 · 研究领域：Cancer Immunotherapy and Biomarkers、Lung Cancer Treatments and Mutations、Lung Cancer Diagnosis and Treatment

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: ) 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....