Ramucirumab or placebo plus erlotinib in EGFR-mutated, metastatic non-small-cell lung cancer: East Asian subset of RELAY

Abstract

In the global phase III RELAY study, ramucirumab plus erlotinib (RAM + ERL) demonstrated superior progression-free survival (PFS) to placebo plus erlotinib (PL + ERL) in untreated patients with epidermal growth factor receptor (EGFR) mutation-positive metastatic non-small-cell lung cancer (NSCLC) (hazard ratio (HR) [95% CI]: 0.59 [0.46-0.76]). This prespecified analysis assessed RAM + ERL efficacy and safety in the RELAY subset enrolled in East Asia (Japan, Taiwan, South Korea, Hong Kong). Randomized (1:1) patients received oral ERL (150 mg/d) plus intravenous RAM (10 mg/kg) or PL Q2W. Primary endpoint was PFS (investigator-assessed). Key secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), overall survival (OS), and safety. Exploratory endpoints included biomarker analyses and time to second progression (PFS2). Median PFS was 19.4 vs 12.5 mo for RAM + ERL (n = 166) vs PL + ERL (n = 170) (HR: 0.636 [0.485-0.833]; P = .0009). The 1-y PFS rate was 72.4% vs 52.2%, respectively. PFS benefit was consistent in most subgroups, including by EGFR mutation (Ex19del, Ex21.L858R). ORR and DCR were similar in both arms, but median DoR was longer with RAM + ERL. OS and PFS2 were immature at data cut-off (censoring rates, 81.2%-84.3% and 64.1%-70.5%, respectively). Grade ≥ 3 treatment-emergent adverse events were more frequent with RAM + ERL (70.7%) than PL + ERL (49.4%). Adverse events leading to treatment discontinuation were similar in both arms (RAM + ERL, 13.3%; PL + ERL, 12.9%), as were post-progression EGFR T790M mutation rates (43%; 50%). With superior PFS over PL + ERL and safety consistent with the overall RELAY population, RAM + ERL is a viable treatment option for EGFR-mutated metastatic NSCLC in East Asia.

Keywords: East Asia; epidermal growth factor receptor; erlotinib hydrochloride; non-small-cell lung cancer; ramucirumab.

FIGURE 1

Kaplan‐Meier plot of progression‐free survival (PFS; investigator‐assessed) in the RELAY East Asian subset. For the analysis of PFS, data for patients who had not had a progression event or had not died at the time of the analysis were censored at the time of their last evaluable assessment (according to the Response Evaluation Criteria in Solid Tumors). CI, confidence interval; ERL, erlotinib; HR, hazard ratio; PL, placebo; RAM, ramucirumab

FIGURE 2

Subgroup analysis of progression‐free survival (investigator‐assessed). The gray column is the width of the 95% confidence intervals (CIs) in the East Asian intention‐to‐treat population. All hazard ratios (HRs) are from unstratified analyses. ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; ERL, erlotinib; PL, placebo; RAM, ramucirumab

FIGURE 3

Kaplan‐Meier plot of progression‐free survival (PFS; investigator‐assessed) in the RELAY East Asian subset in patients with (A) the EGFR exon 19 deletion mutation at baseline and (B) the EGFR exon 21 point mutation at baseline. For the analysis of PFS, data for patients who had not had a progression event or had not died at the time of the analysis were censored at the time of their last assessment (according to the Response Evaluation Criteria in Solid Tumors) that could be evaluated. CI, confidence interval; ERL, erlotinib; HR, hazard ratio; PL, placebo; RAM, ramucirumab