Effectiveness and Safety of Apatinib Plus Chemotherapy as Neoadjuvant Treatment for Locally Advanced Gastric Cancer
Authors: Jian-Xian Lin, Yan-Chang Xu, Wei Lin, Fang-Qin Xue, Jian-Xin Ye, Wei-Dong Zang, Li-Sheng Cai, Jun You, Jian-Hua Xu, Jian-Chun Cai, Yi-Hui Tang, Jian-Wei Xie, Ping Li, Chao-Hui Zheng, Chang-Ming Huang
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Apatinib is a novel treatment option for chemotherapy-refractory advanced gastric cancer (GC), but it has not been evaluated in patients with locally advanced GC. <h3>Objective</h3> To investigate the effectiveness and safety of apatinib combined with S-1 plus oxaliplatin (SOX) as a neoadjuvant treatment for locally advanced GC. <h3>Design, Setting, and Participants</h3> This multicenter, prospective, single-group, open-label, phase 2 nonrandomized controlled trial was conducted in 10 centers in southern China. Patients with M0 and either clinical T2 to T4 or N+ disease were enrolled between July 1, 2017, and June 30, 2019. Statistical analysis was performed from December 1, 2019, to January 31, 2020. <h3>Interventions</h3> Eligible patients received apatinib (500 mg orally once daily on days 1 to 21 and discontinued in the last cycle) plus SOX (S-1: 40-60 mg orally twice daily on days 1 to 14; oxaliplatin: 130 mg/m<sup>2</sup>intravenously on day 1) every 3 weeks for 2 to 5 cycles. A D2 gastrectomy was performed 2 to 4 weeks after the last cycle. <h3>Main Outcomes and Measures</h3> The primary end point was R0 resection rate. Secondary end points were the response rate, toxic effects, and surgical outcome. <h3>Results</h3> A total of 48 patients (mean [SD] age, 63.2 [8.2] years; 37 men [77.1%]) were enrolled in this study. Forty patients underwent surgery (38 had gastrectomy, and 2 had exploratory laparotomy), with an R0 resection rate of 75.0% (95% CI, 60.4%-86.4%). The radiologic response rate was 75.0%, and T downstaging was observed in 16 of 44 patients (36.4%). The pathological response rate was 54.2% (95% CI, 39.2%-68.6%); moreover, this rate was significantly higher in patients who achieved a radiologic response compared with those who did not (12 [80.0%] vs 1 [20.0%];<i>P</i> = .03) and in those who had an Eastern Cooperative Oncology Group Performance Status score of 0 (20 [76.9%] vs 10 [45.5%];<i>P</i> = .03) or had tumors located in the upper one-third of the stomach (16 [61.5%] vs 7 [31.8%];<i>P</i> = .04). Patients who achieved a pathological response (vs those who did not) had significantly less blood loss (median [range]: 60 [10-200] mL vs 80 [20-300] mL;<i>P</i> = .04) and significantly more lymph nodes harvested (median [range]: 40 [24-67] vs 32 [19-51];<i>P</i> = .04) during surgery. Postoperative complications were observed in 7 of 38 patients (18.4%). Grade 3 toxic effects occurred in 16 of 48 patients (33.3%), and no grade 4 toxic effects or preoperative deaths were observed. <h3>Conclusions and Relevance</h3> This nonrandomized controlled trial found that apatinib combined with SOX was effective and had an acceptable safety profile as a neoadjuvant treatment for locally advanced GC. A large-scale randomized clinical trial may be needed to confirm the findings. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT03192735