CYRAMZA® is a human vascular endothelial growth factor receptor 2 (VEGFR2) antagonist indicated:...in combination with erlotinib, for first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations.

EGFR EXON 19 DELETION OR L858R MUTATIONS….Progression on erlotinib (± ramucirumab or bevacizumab), afatinib, gefitinib, or dacomitinib….SUBSEQUENT THERAPY...Continue erlotinib (± ramucirumab or bevacizumab) or afatinib or gefitinib or dacomitinib (if T790M-).

The aim of this paper was to report efficacy and tolerability findings for the Taiwanese participants of RELAY....Patients were enrolled between 28 January 2016 and 1 February 2018 across 100 investigator sites. Key inclusion criteria for patient enrolment included age at least 18 years (at least 20 years in Taiwan), stage IV NSCLC, EGFR mutation-positive (exon 19 deletion or exon 21 [L858R] substitution)...Median PFS for RAM+ERL/ERL+PBO, respectively, was 22.05 months/13.40 months (unstratified hazard ratio 0.4; 95% confidence interval 0.2-0.9); ORR was 92%/60%; median DoR was 18.2 months/12.7 months.

Median PFS was 19.4 vs. 11.2 months for RAM+ERL vs. PL+ERL treatment (hazard ratio [HR]: 0.610; 95% confidence interval [CI]: 0.431-0.864) in the Japanese intent-to-treat population, 16.6 vs. 12.5 months (HR: 0.701 [0.424-1.159]) in the EGFR exon 19 deletion subgroup, and 19.4 vs. 10.9 months (HR: 0.514 [0.317-0.835]) in the EGFR exon 21 L858R subgroup, respectively....Clinically meaningful efficacy was observed with RAM+ERL vs. PL+ERL in the RELAY Japanese subset, with no new safety concerns.

Randomized (1:1) patients received oral ERL (150 mg/day) plus intravenous RAM (10 mg/kg) or PL Q2W...PFS benefit was consistent in most subgroups, including by EGFR mutation (Ex19del, Ex21.L858R)...RAM+ERL is a viable treatment option for EGFR-mutated metastatic NSCLC in East Asia.

...patients were aged 18 years or older (20 years or older in Japan and Taiwan) at the time of study entry, had stage IV NSCLC, with an EGFR exon 19 deletion (ex19del) or exon 21 substitution (Leu858Arg) mutation...progression-free survival was significantly longer in the ramucirumab plus erlotinib group (19·4 months [95% CI 15·4–21·6]) than in the placebo plus erlotinib group (12·4 months [11·0–13·5]), with a stratified hazard ratio of 0·59 (95% CI 0·46–0·76; p<0·0001)....Ramucirumab plus erlotinib demonstrated superior progression-free survival compared with placebo plus erlotinib in patients with untreated EGFR-mutated metastatic NSCLC.

Eligible for first-line treatment with erlotinib based on documented evidence of tumor harboring an activating EGFR mutation [exon 19 deletion or exon 21 (L858R) substitution mutation].

The median PFS of patients who had a ramucirumab or placebo dose adjustment was 20.8 months (95% CI 17.8–22.2) for ramucirumab and 13.9 months (95% CI 12.4–19.3) for placebo...the RELAY trial supports that RAM + ERL...as reflected by the 7-month increase in median PFS for patients in the RAM + ERL arm compared with those in the PBO + ERL arm...RAM + ERL offers a tolerable and effective option for the first-line treatment of EGFR exon 19 deletion or exon 21 (L858R) mutation-positive metastatic NSCLC.

Four studies evaluated bevacizumab + erlotinib (ARTEMIS, NEJ026, J025667, Stinchcombe et al.), and another evaluated ramucirumab + erlotinib (RELAY). These five eligible studies included 1230 non-squamous NSCLC patients, 654 (53.2%) with exon 19 deletion (ex19del) and 568 (46.8%) with EGFRL858R....The combination (anti-VEGF + erlotinib) was significantly associated with prolonged PFS (hazards ratio [HR] 0.59 [95% confidence interval (CI) 0.51–0.69]; p < 0.00001)....For patients with untreated, advanced, EGFR-mutation-harboring NSCLCs, the anti-VEGF + erlotinib combination, compared to erlotinib alone, was associated with significantly prolonged PFS but mature data for OS are needed to confirm the benefit of this strategy.