Anti-VEGF target therapy is proven to be effective both in second and third line treatment in metastatic gastric cancer. As for Apatinib, which is the tyrosine kinase inhibitor showed highly affinity for VEGFR2, could not only reverse paclitaxel resistance but also improve the R0 resection rate in previous unresected gastric cancer in conversional settings. However, the safety and efficacy of Apatinib in combination with docetaxel plus S1 in the first line treatment of metastatic gastric cancer is unknown and worthy of investigation.
The study was expected to enroll 48 patients diagnosed with metastatic gastric cancer. Each participant was supposed to finish six cycles of chemotherapy plus apatinib (docetaxel 75mg/m2, d1, Q3W; S1 according to BSA: <1.25 40mg po bid; 1.25∼1.5 50mg po bid; >1.5 60mg po bid; d1-14, Q3W; apatinib 500mg po qd). The toxicity was determined according to CTCAE 4.0. Efficacy assessed every two cycles (6 weeks) during the study and every 2 months after finish the study. The primary endpoint was progression free survival (PFS). The secondary endpoint was OS, the objective response rate (ORR), the disease control rate (DCR). The tumor response was determined according to RECIST 1.1 criteria.
From July 2017 to April 2019, 32 patients were enrolled. 11 female and 21 male, median age 54 years old, median matastasis organs are 3.5. 80% patients reported adverse events (AEs), most of them are 1-2 AEs. The incidence of grade 3-4 AEs was 35.7%, mainly oral mucositis (23.3%) and myelosuppression (21.5%). For ITT polulation, 24 patients were evaluable for response, 13 patients achieved PR, 4 patients achieved SD, 7 patients experienced PD. The ORR is 54.2%, the DCR is 70.8%. 8 out of 11 per protocol patients have reached primary endpoint, the median PFS is near 6.5 month.
Combination therapy with docetaxel and S1 plus apatinib as the first line treatment could be well tolerant, the spectrum of toxicity were not exceeding expectation. This modality also exhibits promising efficacy,which might provide a new therapeutic strategy for metastatic gastric cancer.
Clinical trial identification
Legal entity responsible for the study
Has not received any funding.
All authors have declared no conflicts of interest.