RELAY, ramucirumab plus erlotinib versus placebo plus erlotinib in patients with untreated, EGFR-mutated, metastatic non-small cell lung cancer: Europe/United States subset analysis. (2021)

• Record Type: Journal Article
• Authors: Ponce Aix, S; Novello, S; Garon, EB; Nakagawa, K; Nadal, E; Moro-Sibilot, D; Alonso Garcia, M; Fabre, E; Frimodt-Moller, B; Zimmermann, AH; Visseren-Grul, CM; Reck, M
• Is Part Of: Cancer treatment and research communications. Number 27(2021)
• Publication Date: 2021
• Subjects: Ethnicity -- Epidermal growth factor receptor -- Phase III -- Regional subset -- Vascular endothelial growth factor
• DOI: 10.1016/j.ctarc.2021.100378
• Languages: English
• ISSNs: 2468-2942

Abstract

Highlights: Ramucirumab+erlotinib showed superior PFS over placebo+erlotinib in the RELAY trial. Activating EGFR mutations are less prevalent in Western populations. Ramucirumab+erlotinib provided similar benefit in Western and overall populations. Results are applicable per the proposed indication, regardless of patient origin. Abstract: Background: In EGFR mutation-positive NSCLC, dual EGFR/VEGFR inhibition compared to EGFR alone increases anti-tumor efficacy. The Phase III RELAY trial demonstrated superior PFS for ramucirumab plus erlotinib (RAM + ERL) over placebo plus erlotinib (PBO + ERL) (HR 0.591 [95% CI 0.461–0.760], p <0.0001). EGFR mutated NSCLC is less prevalent in Western versus Asian patients. This prespecified analysis evaluates efficacy and safety of RAM + ERL in EU and US patients enrolled in RELAY. Patients and Methods: Patients were randomized 1:1 to ERL + RAM (10 mg/kg IV) or PBO Q2W. Treatment continued until unacceptable toxicity or progressive disease. Patients were stratified by geographic region (East Asia vs "other" [EU/US and Canada (EU/US)]). Objectives included PFS, ORR, DoR, OS, PFS2, safety and biomarker analysis. Results: EU/US subset included 113/449 (25.9%) patients (58 RAM + ERL, 55 PBO + ERL). RAM + ERL improved PFS (20.6 vs 10.9 months, HR 0.605 [95% CI: 0.362–1.010]). ORR and DCR were similar, but median DoR was longer with RAM + ERL (18.0 vs 10.1 months, HR 0.527 [95% CI: 0.296–0.939]). OS and PFS2 were immature at data cut-off (censoring rates 81.0–81.8% and 67.3–79.3%, respectively). Most commonly reported Grade ≥3 TEAE for RAM + ERL was hypertension (17 [29.8%]) and for PBO + ERL, dermatitis acneiform (5 [9.1%]). Conclusion: EU/US subset analysis showed improved efficacy outcomes for RAM + ERL and a safety profile consistent with the overall population. Ramucirumab is a safe and effective addition to standard-of-care EGFR-TKI for EGFR mutation-positive metastatic NSCLC.