Thread by @StephenVLiu

#ESMO20 Results from the randomized, double blind ACTIVE trial (CTONG 1706) of apatinib + gefitinib (vs placebo + gefitinib) as 1L treatment for #EGFR mutant NSCLC. Apatinib is a VEGFR2 TKI. Inevitable parallels to RELAY (erlotinib + ramucirumab). #LCSM @OncoAlert

#ESMO20 Treatment naive EGFR+ mNSCLC randomized to oral apatinib 500mg qday or placebo, both with gefitinib 250mg qday. Stratified by mutation, sex, PS. Primary endpoint PFS. #LCSM @OncoAlert

#ESMO20 The ACTIVE trial randomized 313 patients with a median follow up of 15.8 months. Brain metastases present in 32.5% of combination group and 26.3% of gefitinib monotherapy (unclear to me if treated or not). #LCSM @OncoAlert

#ESMO20 Addition of apatinib to gefitinib improved PFS (13.7 vs 10.2 with gefitinib alone), PFS HR 0.71, p=0.0189. Benefit seen across most subgroups. RR similar but duration and depth favored apatinib combination.

#ESMO20 Addition of apatinib to gefitinib did increase toxicity. More G3+ AEs (84.1% vs 37.7%) and dose reductions quite common with apatinib (48.4%) but only 5% discontinued due to AEs. #LCSM @OncoAlert

#ESMO20 Biomarker studies suggest particular benefit to adding apatinib to gefitinib in tumors with TP53 mutations, especially exon 8. These are pretty small sample sizes though. T790M as frequent in both cohorts - important for sequencing strategists. #LCSM @OncoAlert

#ESMO20 Overall, addition of apatinib (VEGFR2 TKI) to gefitinib improves PFS (HR 0.71) at the cost of more toxicity. Unclear impact on survival. A potential option with similarities to RELAY (erlotinib + ramucirumab) but unclear role where osimertinib is the standard. #LCSM