RELAY: Global Ph3 study of erlotinib + ramucirumab or placebo in metastatic NSCLC with EGFR mutation - East Asian subset

Abstract

Background: Dual blockade of the EGFR and VEGFR pathways in EGFR mutation-positive NSCLC is more effective than EGFR inhibition alone. EGFR mutations occur in 10-20% of Caucasian and 40-60% of East Asian (EA) patients (pts) with NSCLC. In the global phase 3 RELAY study (NCT02411448), ramucirumab + erlotinib (RAM+ERL) significantly improved progression-free survival (PFS) compared with placebo + erlotinib (PL+ERL) in pts with EGFR mutation-positive metastatic NSCLC. Here we report efficacy and safety results for the EA subset. Method(s): Previously untreated pts with metastatic NSCLC and EGFR exon 19 deletions or an exon 21 substitution mutation (L858R) were randomized (1:1) to receive ERL (150 mg/day) plus RAM (10 mg/kg Q2W) or placebo until disease progression or unacceptable toxicity. PFS (investigator-assessed, primary endpoint), duration of response (DoR), PFS2 (time to second disease progression), overall survival (OS), and safety were assessed. Result(s): Of 449 pts randomized from Jan 2016 to Feb 2018, 336 pts (75%) were from East Asia (Japan: 211; Taiwan: 56; Korea: 54; Hong Kong: 15). In the RAM+ERL (n = 166)/PL+ERL (n = 170) arms in the EA subset, 64.5%/64.1% were female, 63.3%/64.1% were never-smokers, and 50.6%/49.4% had exon 19 deletions. RAM+ERL improved PFS (median: 19.4 [95% CI 15.2-22.0] vs 12.5 [95% CI 11.1-13.9] months; hazard ratio [HR]: 0.636, 95% CI 0.485-0.833, P = 0.0009) and DoR (median: 16.2 [95% CI 13.8-19.8] vs 11.1 [95% CI 9.7-12.5] months; HR: 0.646, 95% CI 0.481-0.868, P = 0.0036) compared with PL+ERL. PFS2 and OS data are immature, with 67.3% and 82.7% of pts censored. Grade >=3 treatment-emergent adverse events reported in > 5% of pts (RAM+ERL vs PL+ERL) were hypertension (21.3% vs 4.7%), dermatitis acneiform (18.3% vs 8.8%), ALT increased (9.1% vs 9.4%), and diarrhea (5.5% vs 1.2%). Conclusion(s): Consistent with the overall RELAY study population, RAM+ERL improved PFS compared with PL+ERL in the EA subset, with a manageable safety profile. This study was sponsored by Eli Lilly Japan K.K. Medical writing assistance was provided by Justine Southby, PhD, CMPP, and Tania Dickson, PhD, CMPP, of ProScribe - Envision Pharma Group, and was funded by Eli Lilly Japan K.K. ProScribe's services complied with international guidelines for Good Publication Practice (GPP3). Copyright © 2019 European Society for Medical Oncology