Neoadjuvant apatinib combined with oxaliplatin and capecitabine in patients with locally advanced adenocarcinoma of stomach or gastroesophageal junction: a single-arm, open-label, phase 2 trial

Abstract

Background Adding anti-angiogenics to neoadjuvant chemotherapy for localized gastric cancer is recognized as a promising strategy, but its clinical value remains to be defined. Methods This single-center, single-arm, phase 2 trial included patients with locally advanced (cT3/4aN+M0) adenocarcinoma of the stomach or gastroesophageal junction (GEJ) who received three cycles of intravenous oxaliplatin (135 mg/m2 on day 1), oral capecitabine (1000 mg/m2 twice daily on days 1 to 14), and oral apatinib for 21 days (250 mg once daily in the first two cycles, and further increased to 500 mg daily in the third cycle based on whether any adverse event of grade 3 or worse occurred), and an additional cycle of oxaliplatin plus capecitabine, followed by gastrectomy with D2 lymphadenectomy. The primary endpoint was the proportion of patients who achieved an objective response according to RECIST version 1.1. Results Between April 28, 2017, and October 23, 2019, 37 patients were screened and 35 participants were included. Of the 32 patients assessable for efficacy and safety, objective responses were achieved in 25 (78.1%; 95% confidence interval [CI], 60.0% to 90.7%) patients. Thirty-one (96.9%) patients received R0 resection, two (6.3%) patients achieved pathological complete response, and 11 (34.4%) patients achieved pathological response. At the data cutoff date (September 30, 2021), the median event-free survival was 42.6 (95% CI, 16.2 to not reached) months, and the median overall survival was not reached. The most common grade 3 or 4 treatment-emergent adverse events were hypertension (9/32, 28.1%), thrombocytopenia (7/32, 21.9%), and neutropenia (5/32, 15.6%). Seven (21.9%) patients developed surgical complications, and the most common one was intra-abdominal abscess (4/32, 12.5%). Conclusions The concomitant use of apatinib, oxaliplatin, and capecitabine as neoadjuvant therapy showed promising efficacy and manageable safety profile in patients with locally advanced adenocarcinoma of the stomach or GEJ, and further phase 3 study is warranted. Trial registration This study was registered with ClinicalTrial.gov (NCT03229096).

Current Status and Research Progress of Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer

“…There was a higher incidence of postoperative anastomotic fistula in the combined bevacizumab treatment group, and the study demonstrated no survival benefit from chemotherapy combined with bevacizumab. In some Chinese studies, neoadjuvant apatinib in combination with chemotherapy followed by surgery has shown good efficacy and a manageable safety profile in patients with locally advanced gastric or GEJ adenocarcinoma [45] [46] [47] the true validity of these non-randomised controlled trials needs to be validated by large RCTs.…”

Response Evaluation after Neoadjuvant Chemotherapy for Resectable Gastric Cancer

“…The first is quantifying the response by measuring any change in tumor size, with the response evaluation criteria in solid tumors (RECIST) being the most frequently used tool [ 13 ]. This method was designed for evaluating solid tumors in a non-curative setting, but it is frequently encountered in scientific reporting on the response to NAC in gastric cancer [ 9 , 25 , 26 , 27 , 28 , 29 ]. It is of great importance to disclose any limitations of downsizing as a concept of the response to NAC in a Western cohort of resectable gastric cancers.…”

Pathological complete remission of a locally advanced gastric cancer by neoadjuvant therapy “sandwich” regimen as SOXAP+ fluorescence laparoscopic surgery +SOXAP: Case report

“…Apatinib is currently the third-line treatment drug for advanced gastric cancer recommended by the CSCO guidelines, and the study of Zheng et al showed that the total pathological effective rate of Apatinib combined with SOX chemotherapy for neoadjuvant treatment of gastric cancer was as high as 89.7% ( Zheng et al, 2020 ). And there is a clinical trial proved that oxaliplatin and capecitabine combined with Apatinib used as new adjuvant therapy, showing good efficacy and manageable safety in patients with LAGC or GEJ ( Tang et al, 2022 ). Zhi et al reported a clinical trials result, Camrelizumab Combined with Chemotherapy Followed by Camrelizumab plus Apatinib as First-line Therapy for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma, which can make GC patients gain FPS and OS benefits, moreover this regime has a manageable toxicity ( Peng et al, 2021 ).…”