Safety Of Apatinib As Third-Line Or Beyond Treatment In Advanced Or Metastatic Gastric Cancer: Results From A Multicenter Phase Iv Study (Ahead-G201).

e16019 Background: An open-label, multicenter, post-marketing Phase IV study of apatinib (Ahead-G201; ClinicalTrials.gov: NCT02426034) is being conducted in a broad range of gastric cancer patients (pts) with a target sample size of 2000+. The interim analysis was released in 2018 Gastrointestinal Cancers Symposium (Abstract #103). Herein, we reported the updated safety data in detail. Methods: Pts with advanced or metastatic adenocarcinoma of stomach or gastro-esophageal junction after at least two lines of chemotherapy were recruited to receive oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. Results: As of 12/21/2017, 1468 pts were enrolled. Median age was 60 yrs; male/female was 72.1/27.9%; ECOG PS 0/1/≥2 was 16.4/65.6/18.0%. The mean dosage was 509.9 mg/d. During the follow-up period, 482 (32.8%) pts had to interrupt administration to manage adverse events (AEs) including hand-foot-skin reaction (HFSR), proteinuria (PTN) and hypertension (HTN). 189 (12.9%) pts lowered dose at least once mainly due to PTN, platelet decrease and HFSR, whereas dose increase occurred in 116 (7.9%) pts according to the protocol mainly owing to good tolerance or improvement in AEs. In total, 6312 drug-related AEs (DRAEs) were reported by 908 (61.9%) pts. The incidence of Grade ≥3 DRAEs was 28.6% (420/1468). The most common DRAEs included HTN (253, 17.2%), PTN (239, 16.3%), leukocyte decrease (216, 14.7%), fatigue (191, 13.0%), platelet decrease (180, 12.3%), HFSR (142, 9.7%) and neutrophil decrease (137, 9.3%). The main DRAEs of Grade ≥3 were HTN (87, 5.9%), platelet decrease (36, 2.5%) and HFSR (35, 2.4%). Typical AEs associated with anti-angiogenetic drugs occurred early following apatinib therapy: HTN was frequently diagnosed in the first 4 weeks, and its incidence decreased gradually; HFSR was commonly detected during the 2nd–5th week, and PTN during the 3rd–7th week. Conclusions: Well-established and manageable safety profile of apatinib and early presence pattern of anti-angiogenesis AEs are reaffirmed in this large clinical practice setting of pts with chemo-refractory advanced or metastatic gastric cancer. Clinical trial information: NCT02426034.