Study on Efficacy and Safety of Low-Dose Apatinib Combined with Camrelizumab and SOX Regimen as First-Line Treatment of Locally Advanced and Unresectable Gastric/Gastroesophageal Junction Cancer: A Protocol for an Open-Label, Dose Escalation and Extension Phase Ib Clinical Trial

Abstract

Background The standard treatment for advanced gastric/gastroesophageal junction cancer (AGC/GEJC) is palliative chemotherapy combined with targeted therapy. The SOX regimen (S-1 plus oxaliplatin) is recommended as neoadjuvant or palliative first-line chemotherapy in Asian patients. Apatinib, an oral VEGFR tyrosine kinase inhibitor, is associated with additional survival benefit as third- or subsequent-line therapy. However, the median overall survival time of AGC/GEJC is only 8–11 months in the West and 13–17 months in East Asia/Japan, even with the application of anti-angiogenic agents. Hence, the multimodal and individual management of patients is challenging standards to improve prognosis, including the preferential use of low-dose anti-angiogenic drugs and immunotherapy, as well as the application of multi-disciplinary treatment (MDT)-directed conversion therapy. Methods/Design This single-center study was designed to combine low-dose apatinib with camrelizumab plus the SOX regimen in diagnosed potentially resectable and initially unresectable AGC/GEJC. This a prospective, open-label, single-arm, dose escalation and extension phase Ib clinical trial, conducted in Jiangsu Province Hospital, beginning from June 2020. All patients will first receive this combined regimen (3 weeks/cycle) for at most eight cycles, then apatinib and camrelizumab in maintenance therapy until disease progression, intolerable toxicity, death, a maximum 2 years of treatment or discontinuation for any reason. Follow-up and evaluation will be carried out regularly. If surgery is allowed by MDT discussions, oral apatinib will be discontinued during the last preoperative cycle. The primary endpoints are the objective response rate and maximum tolerated dose according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) and the Common Terminology Criteria for Adverse Events (CTCAE) criteria (version 5.0). Discussion This study will assess the response and side effects of AGC/GEJC patients in the use of low-dose apatinib combined with camrelizumab and the SOX regimen, and this combined therapy is expected to be a feasible and optimized first-line treatment option. In addition, this study will provide robust evidence and novel ideas for conversion therapy. Trial Registration ChiCTR.gov.cn: ChiCTR2000034109.

Meta-Analysis of Efficacy and Safety of Karelizumab Combined with Apatinib in the Treatment of Advanced Gastric Cancer

“…After the duplicate literatures were eliminated, the titles and abstracts of the literatures were read. Based on the inclusion criteria and exclusion criteria, 20 literatures were finally included in this systematic analysis [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. The screening process is shown in Figure 1.…”

“…All the included 20 literatures [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] reported DCR, and the heterogeneity among 20 studies was low (P = 0:87, I 2 = 0%). The fixed effect model was used to analyze the data, which showed that the ROO of gastric cancer patients in the observation group was significantly higher than that in the blank group (OR = 3:09, 95% CI [2.29, 4.16], P < 0:01), as recorded in Figure 4 for details.…”

“…Literature Quality. Review Manager 5.3 software was used to evaluate the literature quality of 20 included[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] literatures by Cochrane risk bias evaluation tool. The overall quality of the 20 included in this study was low.…”

Low-dose apatinib combined with camrelizumab and the SOX regimen in the neoadjuvant treatment of locally advanced gastric/gastroesophageal junction adenocarcinoma (SPACE-neo): a protocol for an open-label, single-arm, clinical trial

“…In 2020, our team carried out a dose escalation and extension phase Ib clinical trial (SPACE) on the first-line treatment of potentially resectable and initially unresectable AGC/GEJC with low-dose apatinib combined with camrelizumab and the SOX regimen ( 20 ). At first, all patients received this combined regimen (3 weeks/cycle) for a maximum of eight cycles, followed by apatinib and camrelizumab as maintenance therapy until discontinuation for any reason.…”

“…Our team then carried out the SPACE study to assess the efficacy and safety of low-dose apatinib combined with camrelizumab and the SOX regimen as a first-line treatment of AGC/GEJC ( 20 ). The preliminary findings of four-drug combination showed an ORR of 94.7%, a disease control rate (DCR) of 100%, and a median PFS (mPFS) of 8.3 months.…”