Efficacy of Conversion Surgery Following Apatinib Plus Paclitaxel/S1 for Advanced Gastric Cancer With Unresectable Factors: A Multicenter, Single-Arm, Phase II Trial

Abstract

Objective: Conversion therapy (surgical resection after chemotherapy) is a promising option for unresectable gastric cancer (GC) patients. Addition of anti-angiogenesis drug improves response to chemotherapy. Hence, this study explored the feasibility and efficacy of preoperative paclitaxel (PTX)/S1 chemotherapy combined with apatinib for unresectable GC.Methods: Thirty-one eligible patients with a single unresectable factor were enrolled in this multi-center, single-arm trial. Apatinib (500 mg qd) was administered continuously, while PTX (130 mg/m2) on day 1 and S1 (80 mg/m2) on day 1–14 were given every 3 weeks. The treatment was given for three cycles preoperatively, but the last cycle did not include apatinib. The primary objective measurements included R0 resection rate, objective response rate (ORR) and morbidity of preoperative treatment.Results: Among the 31 patients, 30 patients were evaluable for tumor response, the ORR to preoperative treatment was 73.3%. Eighteen of 30 patients underwent surgery, and R0 resection was achieved in 17 patients. The patients who underwent the conversion surgery had a superior OS compared with those who did not (3 years OS: 52.9 vs 8.3%, p = 0.001). The surgery was operated after apatinib had stopped for a median duration of 4 weeks. Neither anastomotic leakage nor wound healing complications was observed. No increased bleeding event was observed compared with historical data. During preoperative treatment, grade 3 or 4 toxicities were experienced by 58.1% of the patients.Conclusion: Chemotherapy in combination with apatinib demonstrated higher rates of conversion and R0 resection and a superior survival benefit in initial unresectable GC. It is safe and reasonable to suspend apatinib for 4 weeks before the gastrectomy.

Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer

“…The reason might lie in that apatinib is a small molecular tyrosine kinase, which has a much shorter half-life (about 9 h) than antibodies (e.g., about 20 days for bevacizumab) 40,41 . Consistent with this, adding apatinib to conversion chemotherapy showed no anastomotic leakage or wound-healing complications in patients with advanced gastric cancer 42 . By comparing baseline pathology and omics data between patients with different responses, we identified potential biomarkers associated with pathological responses.…”

Conversion Therapy in Gastric Cancer – Curative Intent in Stage IV Patients is Beneficial

“…[16,19,24,28,31] Few investigators have studied the role of speci c chemotherapy regimens, but there is no head to head comparison of different regimens. [22,32,33] The present study showed a signi cant survival advantage of EOX and DOX regimen over FLOT, but this could be biased due to the small sample size. Institutional guidelines may be followed in deciding the optimal chemotherapy regimen for conversion therapy.…”

Efficacy and Safety of Apatinib plus Neoadjuvant Chemotherapy for Locally Advanced Esophageal Squamous Cancer: A Phase II Trial

“…Antiangiogenic therapy was associated with potentially serious toxic effects, such as gastrointestinal perforation, hemorrhage, and delayed wound-healing, presenting additional challenges to neoadjuvant chemotherapy. Previous clinical trials had shown that patients with several solid tumors receive apatinib at dose of 500-850 mg/day [ 20 ]. Considering the toxicity of TP, we used 425 mg/day as the initial dose of apatinib in this study.…”