Effect of apatinib plus neoadjuvant chemotherapy followed by resection on pathologic response in patients with locally advanced gastric adenocarcinoma: A single-arm, open-label, phase II trial
Yanan Zheng, Xiao Yang, Chao Yan, Runhua Feng, Birendra Kumar Sah, Zhongyin Yang, Zhenglun Zhu, Wentao Liu, Wei Xu, Zhentian Ni, Maneesh Kumarsing Beeharry, Zichen Hua, Min Yan, Zhenggang Zhu, Chen Li, Yanan Zheng, Xiao Yang, Chao Yan, Runhua Feng, Birendra Kumar Sah, Zhongyin Yang, Zhenglun Zhu, Wentao Liu, Wei Xu, Zhentian Ni, Maneesh Kumarsing Beeharry, Zichen Hua, Min Yan, Zhenggang Zhu, Chen Li
Abstract
Background: The evidence of combining neoadjuvant chemotherapy with targeted therapy for patients with locally advanced gastric cancer is inadequate. We conducted a single-arm phase II trial to evaluate the efficacy and safety of S-1, oxaliplatin and apatinib (SOXA) in patients with locally advanced gastric adenocarcinoma.
Methods: Treatment-naïve patients received three preoperative cycles of S-1 (80-120 mg/day on days 1-14) and oxaliplatin (130 mg/m2 on day 1) and two cycles of apatinib (500 mg/day for 21 days) at 3-week intervals, followed by surgery. The primary end-point was pathologic response rate (pRR). This trial is registered at ChiCTR.gov.cn: ChiCTR-OPC-16010061.
Results: Of 29 patients included, median age was 60 (range, 43-73) years; 20 (69.0%) were male. The pRR was 89.7% (95% confidence interval [CI], 72.7%-97.8%; 26 of 29 patients; P < 0.001) with 28 patients treated with surgery. All 29 patients were available for preoperative response evaluation, achieving an objective response rate of 79.3% (95% CI, 60.3%-92.0%) and a disease control rate of 96.6% (95% CI, 82.2%-99.9%). The margin-free resection rate was 96.6% (95% CI, 82.2%-99.9%). The pathologic complete response rate was 13.8% (95%CI, 1.2%-26.3%). Downstaging of overall TNM stage was observed in 16 (55.2%) patients. During neoadjuvant therapy, 10 (34.5%) patients had grade ≥III adverse events. No treatment-related death occurred. Surgery-related complications were observed in 12 of 28 (42.9%) patients.
Conclusion: SOXA followed by surgery in patients with locally advanced gastric adenocarcinoma showed favourable activity and manageable safety. A randomised controlled trial in locally advanced gastric or oesophagogastric junction adenocarcinoma is ongoing (ClinicalTrials.gov: NCT04208347).
Keywords: Apatinib; Gastric cancer; Neoadjuvant therapy; Oxaliplatin; S-1.
Conflict of interest statement
Conflict of interest statement All authors declare that they have no conflict of interest.
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
Source: PubMed