Efficacy and safety of neoadjuvant chemoradiotherapy plus apatinib for patients with locally advanced, HER2-negative, Siewert's type II-III adenocarcinoma of esophagogastric junction: a single-arm, open-label, phase II trial

Abstract

This study aimed to investigate the efficacy and safety of concurrent neoadjuvant chemoradiotherapy (CRT) plus apatinib in treating locally advanced, HER2-negative, Siewert's type II-III adenocarcinoma of esophagogastric junction (AEG) patients. Thirty eligible patients were analyzed in this single-arm, open-label, phase II trial. Patients received neoadjuvant regimen as follows: two cycles of apatinib (orally, 250 mg/day on day 1-28), two cycles of capecitabine (orally, 1,000 mg/m2 twice daily on day 1-14), oxaliplatin (intravenously, 130 mg/m2 on day 1), and concurrent radiotherapy (a total dose of 45 Gy in 25 fractions) started on day 1 of chemotherapy. Then, surgery was performed within 8-12 weeks after the completion of neoadjuvant therapy. This trial was registered on the ClinicalTrials.gov website (access number: NCT03349866). After neoadjuvant CRT plus apatinib treatment, 18 (60.0%) patients achieved objective response, 29 (96.7%) patients achieved disease control, and 20 (66.7%) patients achieved down-staging. Encouragingly, tumor regression grade (TRG) 0, TRG 1, TRG 2 and TRG 3 were observed in 33.3%, 20.0%, 30.0% and 10.0% patients, respectively; the pathological complete response rate was 33.3%, and the R0 resection rate was 93.3%. Regarding survivals, the 1-year and 2-year progression-free survival rates were 96.7% and 88.1%, respectively. Meanwhile, the 1-year and 2-year overall survival rates were 100.0% and 96.6%, respectively. As to safety, the majority of the adverse events were of mild grade, and the post-operative complications were manageable. In conclusion, neoadjuvant CRT plus apatinib exhibits high efficacy and acceptable tolerance in patients with locally advanced, HER2-negative, Siewert's type II-III AEG.

Keywords: Neoadjuvant chemoradiotherapy; adenocarcinoma of esophagogastric junction; apatinib; efficacy; safety.

Conflict of interest statement

None.

AJTR Copyright © 2021.

Figures

Figure 1

Study flow chart. AEG, adenocarcinoma of esophagogastric junction; CT, computerized tomography; CRT, chemoradiotherapy; MRI, magnetic resonance imaging.

Figure 2

Treatment response to neoadjuvant CRT plus apatinib. CRT, chemoradiotherapy; AEG, adenocarcinoma of esophagogastric junction; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR, disease control rate.

Figure 3

Pathological response. Tumor regression grade (A), pCR rate and R0 resection rate (B) in response to neoadjuvant CRT plus apatinib treatment. pCR, pathological complete response; CRT, chemoradiotherapy; AEG, adenocarcinoma of esophagogastric junction.

Figure 4

PFS and OS. The PFS (A) and OS (B) shown by Kaplan-Meier curve. PFS, progression-free survival; OS, overall survival.