A multi-center, single-arm, phase II study of anlotinib plus paclitaxel and cisplatin as the first-line therapy of recurrent/advanced esophageal squamous cell carcinoma

• Published in: BMC medicine Vol. 20; no. 1; p. 472
• Main Authors: Li, Ning, Wu, Tao, Hong, Yong-Gui, Guo, Yan-Zhen, Cheng, Yu-Feng, Ma, Yi-Jie, Bie, Liang-Yu, Cui, Dong-Hai, Gao, Xiao-Hui, Tan, Bing-Xu, Li, Bao-Sheng, Luo, Su-Xia, Wang, Jun-Sheng
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08.12.2022; BioMed Central; BMC
• Subjects: Advanced esophageal squamous cell carcinoma; Angiogenesis; Anlotinib; Anticancer properties; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antitumor agents; Biomarkers; Bone marrow; c-Kit protein; Cancer; Cancer therapies; Chemotherapy; China; Cisplatin; Cisplatin - therapeutic use; Clinical medicine; Clinical trials; Disease control; Dosage and administration; Drug therapy; Drug therapy, Combination; Effectiveness; Efficacy; Esophageal cancer; Esophageal Neoplasms - drug therapy; Esophageal Squamous Cell Carcinoma - drug therapy; Ethics; Growth factors; Health services; Humans; Intravenous administration; Kinases; Medical prognosis; Metastases; Metastasis; Myelosuppression; Neutropenia; Paclitaxel; Paclitaxel - therapeutic use; Patients; Protein-tyrosine kinase; Relapse; Safety; Safety management; Squamous cell carcinoma; Subgroups; Survival; Testing; Therapy; Toxicity; Tumors; Tyrosine; Vomiting; China; Anlotinib; First-line therapy; Paclitaxel; Efficacy; Safety; Cisplatin; Advanced esophageal squamous cell carcinoma
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-022-02649-x

Anlotinib, a tyrosine kinase inhibitor, has shown encouraging anti-tumor activity in esophageal squamous cell carcinoma (ESCC). This study was designed to assess the efficacy and safety of anlotinib plus paclitaxel and cisplatin (TP) as first-line therapy for advanced ESCC. In a multi-center, single-arm, phase II clinical trial, patients (aged > 18 years) with ESCC, which was judged to be locally advanced, recurrent, or metastatic, received 10 mg oral anlotinib once daily on days 1-14, 135 mg/m intravenous paclitaxel on day 1, and 60-75 mg/m intravenous cisplatin on days 1-3 every 3 weeks for a maximum of 4-6 cycles as the initial therapy in five centers in China. Subsequently, patients received anlotinib monotherapy (10 mg) as maintenance therapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Forty-seven patients were enrolled in this study between October 2019 and March 2021. The median follow-up was 14.04 months (IQR, 9.30-19.38). Of 46 with assessable efficacy, the median PFS and median overall survival were 8.38 months (95% CI, 6.59-10.17) and 18.53 months (95% CI, 13.11-23.95), respectively. The objective response rate was 76.1% (95% CI, 61.2-87.4%), with 4 (8.7%) complete responses and 31 (67.4%) partial responses. The disease control rate was 91.3% (95% CI, 79.2-97.6%). The median duration of response was 6.80 months (95% CI, 4.52-9.08), and 1 patient had an ongoing response for 23 months. Subgroup analysis revealed no association between clinical factors and survival or response. Of the 47 patients with assessable safety, the main grade ≥ 3 treatment-emergent adverse events (TEAEs) were neutropenia (17.0%), bone marrow suppression (12.8%), and vomiting (10.6%). No treatment-related deaths or serious TEAEs were observed. Notably, higher c-Kit levels were an independent factor for superior PFS (HR = 0.032; 95% CI, 0.002-0.606; P = 0.022). The study demonstrated a manageable safety profile and durable clinical response of anlotinib plus TP as first-line therapy in advanced ESCC, which suggested a potential therapeutic option for this population. ClinicalTrials.gov NCT04063683. Registered 21 August 2019.