Blocking vascular endothelial growth factor receptor (VEGFR) pathway can enhance the efficacy of EGFR-TKI in EGFRm NSCLC. ACTIVE is the first phase III study evaluating apatinib, an oral small molecule VEGFR2-TKI, or placebo plus gefitinib as first-line therapy in patients (pts) with EGFRm NSCLC.
Treatment-naïve pts with classic EGFR mutation (ex19del or L858R) were randomized (1:1) to receive once-daily oral apatinib 500 mg plus gefitinib 250 mg (AG arm) or placebo plus gefitinib 250 mg (G arm). Stratification factors: EGFR mutation type (ex19del, L858R), sex, and performance status (0, 1). The primary endpoint was PFS (RECIST 1.1) assessed by blinded independent radiology review committee (IRRC). Secondary endpoints: PFS by investigator (INV), OS, ORR, DCR, DOR, TTPD, QoL and safety. Next-generation sequencing (NGS) was used to analyze baseline and post-progression samples for exploring efficacy predictors and acquired resistance.
313 pts were enrolled (AG arm, n=157; G arm, n=156). Median follow-up was 15.8 months (IQR 12.6, 20.4). Median PFS by IRCC was 13.7 versus 10.2 months in AG and G arms (HR = 0.71, 95% CI 0.54-0.95; p = 0.0189). Prolonged PFS by INV (HR = 0.71, 95% CI 0.53-0.95) was observed. OS data are immature at cutoff (29.4% events). ORR was 77.1% and 73.7% in AG and G arms (p = 0.5572). Pts with ex19del had better HR than L858R (HR = 0.67, 0.45-0.99; 0.72, 0.48-1.09). NGS results of baseline samples showed a marginally significant improved PFS in
Apatinib plus gefitinib as first-line therapy demonstrated superior PFS.
NCT02824458.
Sun Yat-sen University Cancer Center.
The 5010 Clinical Research Foundation of Sun Yat-sen University; Jiangsu Hengrui Medicine Co., Ltd.
All authors have declared no conflicts of interest.