Regorafenib vs. apatinib: An indirect treatment comparison in the treatment of advanced gastric cancer.

Abstract

e16082 Background: Advanced gastric cancer has a poor prognosis with limited treatment options. The mainstay of treatment is chemotherapy with targeted therapy (HER2, VEGF pathway) and immunotherapy added to it based on markers. Although, the objective response rate is 40 to 60% and disease control rate is 60 to 70%, median overall survival continues to be < 2 years or possibly lower in patients with poor performance status. Tyrosine kinase inhibitors which target the VEGF pathway have been shown to improve overall survival and progression free survival in these patients. No head-to-head comparison has been performed between these agents in this patient population. Methods: Data pertaining to the INTEGRATE IIA (regorafenib vs. best supportive care) and NCT01512745 (apatinib vs. best supportive care) clinical trials was analyzed. INTEGRATE IIA was a phase 3 randomized double-blind placebo controlled clinical trial with 2:1 randomization and NCT01512745 was a phase 3 randomized double-blind placebo controlled clinical trial with 2:1 randomization. In both studies patients had failed > 2 prior therapies. The best supportive care arm was used as the common comparator. Patient population characteristics were compared along with treatment adverse events. Hazard ratios for overall survival and progression free survival were compared using the Bucher method for indirect treatment comparison. Upper and lower limits of the 95% confidence intervals were calculated. Results: Indirect treatment comparison of regorafenib and apatinib shows a hazard ratio of 0.99 for overall survival and a hazard ratio of 1.19 for progression free survival. However, these results are not statistically significant: 95% confidence interval for overall survival was 0.69 to 1.41 and 95% confidence interval for progression free survival was 0.8 to 1.79. Results are tabulated below. Although, > 2/3rds of the patients in the INTEGRATE IIA clinical trial were from Asia, baseline characteristics could not be appropriately matched as the NCT01512745 clinical trial was conducted in China. These results suggest that apatinib and regorafenib have similar efficacy but apatinib may show slightly better progression free survival. These results are pertinent as apatinib is better tolerated than regorafenib due to a better side effect profile. Conclusions: Apatinib and regorafenib appear to have similar efficacy in terms of overall survival and progression free survival. Apatinib has a better side effect profile and may be considered as a preferred alternative to regorafenib. Direct comparison of these two agents, possibly with a lower dose of regorafenib may be considered for a future clinical trial. Regorafenib vs. Best Supportive Care (INTEGRATE IIA) Apatinib vs. Best Supportive Care (NCT01512745) Indirect Treatment Comparison OS 0.7 (0.56 – 0.87) 0.709 (0.537 – 0.937) 0.99 (0.69 - 1.41) PFS 0.53 (0.4 to 0.7) 0.444 (0.331 – 0.595) 1.19 (0.8 - 1.79)