P-082Efficacy and safety of intermittent dosing schedule of apatinib for advanced gastric cancer in second-line setting

Introduction: To explore optimal dosing strategy of apatinib treatment in advanced gastric cancer, this study was conducted to compare the efficacy and safety of intermittent (5 days on/2 days off schedule) vs continuous apatinib therapy in combination with docetaxel as second-line treatment for advanced gastric cancer. The design of this study was released in ESMO WCGI 2018 Congress. Methods: This was an open-label, randomized, clinical trial. Eligible patients were randomized to receive intermittent or continuous dosing schedule in a ratio of 1:1. In the intermittent dose arm, patients received oral apatinib 500 mg/d for 5 days followed by 2 days off treatment. In the continuous dose arm, patients received oral apatinib 500 mg/d as continuous daily dosing. Docetaxel 60 mg/m2 was administered intravenously to patients on day 1 in a 21-day cycle in both groups. The primary outcome was progression-free survival. The secondary outcomes included tumor response, overall survival, quality of life and safety. Results: Between September 15, 2017 and January 15, 2019, 58 patients (pts) were enrolled, and 54 were eligible for the analysis, 28 in the intermittent dosing group and 26 in the continuous dosing group. The baseline characteristics of the two groups were balanced. The male pts were 18 (64.29%) in intermittent dosing group versus 18 (69.23%) in continuous dosing group. The patients with ECOG PS 0-1 were 28 (100%) versus 24 (92.31%). Twelve pts experienced surgery (42.86%) versus 14 (53.85%), and 6 (22.22%) versus 13 (50.00%) pts had more than 2 metastases. A total of 37 pts were eligible for short-term efficacy evaluation. The best tumor responses were as follows: in the intermittent dosing group, no one achieved complete response (CR), 5 achieved partial response (PR), 8 achieved stable disease (SD) and 7 achieved progressive disease (PD); in the continuous dosing group, 1 achieved CR, 1 achieved PR, 9 achieved SD, and 6 achieved PD. The overall response rate was 25% versus 11.76%, and disease control rate was 65% versus 64.71%. The mPFS were 5.15 months (95% CI, 2.20-6.26) versus 5.44 months (95% CI, 1.64-6.13), P = .65. The mOS was not reached in the intermittent dosing group, and the mOS in continuous dosing group was 9.80 months (95% CI, 3.08-9.80 +), P = .58. There were 2 pts who experienced dose reduction due to toxicities in the two groups, respectively. The incidence of all grade AEs was 95.83% versus 100%. The incidence of non-hematological AEs was 66.67% versus 100%, and the difference was statistically significant (P = .005). The incidence of hematological AEs was 40.91% versus 100%, and the difference was statistically significant (P = .005). The incidence of grade≥3 AEs was 2% versus 12.96%. No grade 4 AE was reported in intermittent dosing group, and 1 grade 4 AE was reported in continuous dosing group. The most frequent AEs were hypertension (29.17%), fatigue (33.33%), proteinuria (25%), hand-foot syndrome (20.83%) in intermittent dosing group, and in the continuous dosing group the most frequent AEs were hypertension (42.11%), fatigue (36.84%), proteinuria (31.58%), hand-foot syndrome (36.84%). Conclusion: The efficacy profiles of these two dosing regimens were comparable. Patients who received the intermittent dosing regimen experienced less AEs, especially grade≥3 AEs. Intermittent dose scheduling of apatinib could exhibit similar efficacy and less toxicity, and could be an alternative for advanced gastric cancer in second-line treatment.