Efficacy and Safety of Apatinib plus Neoadjuvant Chemotherapy for Locally Advanced Esophageal Squamous Cancer: A Phase II Trial.

ABSTRACT

Evidence for neoadjuvant chemotherapy combined with targeted therapy for locally advanced esophageal squamous cancer (ESCC) is inadequate. We conducted a single-arm phase II trial to evaluate the efficacy and safety of apatinib combined with taxol and cisplatin (ATP) for locally advanced ESCC. All patients were cT3-4aN0-3 M0 (IIIb-IVa) stage, which were confirmed by histopathology. Apatinib was taken orally (425 mg/d) for two cycles, followed by one cycle of rest. Taxol was administered at 135 mg/m2 intravenously on day 1, and cisplatin was administered at 20 mg/m2 intravenously on day 1 to day 3. Radical ESCC resection was performed 4 weeks after ATP. The primary endpoint was pathological response rate (pCR). Secondary endpoints were pathologic response rate (MPR), disease-free survival (DFS), overall survival (OS), R0 resection rate, and safety profile. This trial was registered. We evaluated 41 patients for screening from Oct 2018 to July 2020, of whom 39 were enrolled in the study, with a median age of 65 years (range 49-75 years), and 29 (74.4%) were male. Among the 39 patients, 1 was considered unresectable by the multidisciplinary team due to tumor progression, and 38 patients underwent surgery eventually. The median follow-up was 22 months (range 5-29 months), and the follow-up rate was 100%. The 1-year and 2-year OS was 95% and 95%, and the 1-year and 2-year DFS was 85% and 82%, respectively. Thirty-eight (97.3%) successfully underwent R0 resection. Of the 38 evaluable patients, 9 (23.6%) were pCR, and 15 (39.5%) were MPR. The most common ATP-related AEs were nausea (76.9%), leucopenia (53.8%), neutropenia (51.2%) and vomit (51.2%), anemia (41.0%), and hypertension (25.6%). The most frequent grade 3-4 events included leucopenia (15.3%), neutropenia (15.3%), nausea (12.8%), vomit (12.8%), and hypertension (10.2%). No treatment-related death occurred. Neoadjuvant apatinib combined with taxol and cisplatin for locally advanced ESCC showed favorable activity and manageable safety.