Apatinib in combination with docetaxel and S1 chemotherapy in the first-line treatment of metastatic gastric cancer.
Authors: Xia Ling , Gao Yu , Gong Jun , Dai Jing , Peng Jin , He Lilin , Chen Weidong , Gong Wei , Yang Lei , Wen-bo Wang , Jiang Huangang , Xu Hui , Wang Qing-Yun , Wu Han , Wang You , Wu Lu , Zhou Fuxiang 
Published: June 2021

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Background: First-line chemotherapy in metastatic gastric cancer, either doublet or triplet-regiment, the average OS is less than one year. Anti-VEGF target therapy is proven to be effective both in second and third line settings. As for apatinib, which is the tyrosine kinase inhibitor showed highly affinity for VEGFR2, is permitted by SFDA to be used in the third line treatment of gastric cancer since September 2014. The post-market stage IV clinic trial Ahead-G201 further confirmed it can improve the OS in chemotherapy-refractory gastric cancer. What’s more, apatinib could reverse paclitaxel resistance and improve the R0 resection rate in conversion of unresected gastric cancer in neoadjuvant 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. Methods: With expectation to improve PFS from 5.3m (the START Study) to 7m, this investigator-initiated, single arm, multi-center, registered phase II prospective study was designed to enroll 48 eligible patients diagnosed with metastatic gastric cancer. Each participant was expected to finish six cycles of chemotherapy plus apatinib (docetaxel 75mg/m2, d1, Q3W; S1 according to BSA: <1.25 40mg po bid; 1.25̃1.5 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 during the follow-up period. The primary endpoint was PFS. The secondary endpoint was OS, ORR, and DCR. The tumor response was determined according to RECIST 1.1 criteria. Results: Baseline characteristics (FAS population): From July 2017 to December 2020, 45 patients from 5 centers across Hubei province were enrolled. Among them, 44 are eligible for analysis. There are 15 females and 30 males, median age 55 years old, median metastasis sites is 2, yet 63.6% of them have involved at least 2 organs. Safety: 90.91% patients reported adverse events (AEs). The incidence of grade 3-4 AEs was 47.73%. Main 3-4 AEs were oral ulceration (13.64%), leucopenia (13.64%), neutropenia (13.64%), hand-foot syndrome (6.82%), hypertension (6.82%), and thrombocytopenia (6.82%). Efficacy: By Jan 31th, 2021, 44 patients were evaluable for response and survival, 26 of them achieved partial response (PR), 9 achieved stable disease (SD), and 8 experienced progression disease (PD). The ORR is 60.47%, the DCR is 81.4%. Median PFS is 7.46m, median OS is 12.42m. So we closed the study in advance. Conclusions: Adding apatinib to standard DS chemotherapy as the first line treatment would be well tolerant in patients with metastatic gastric cancer, the spectrum of toxicity were not exceeding expectation. This modality also exhibits prolonged PFS, which might provide an alternative therapeutic strategy for metastatic gastric cancer. Clinical trial information: NCT03154983.