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

• Published in: Cancer treatment and research communications Vol. 27; p. 100378
• Main 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
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 2021; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Brain Neoplasms - secondary; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - secondary; Double-Blind Method; Drug Eruptions - etiology; Epidermal growth factor receptor; ErbB Receptors - genetics; Erlotinib Hydrochloride - administration & dosage; Ethnicity; Europe; Female; Humans; Hypertension - chemically induced; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Middle Aged; Mutation; Phase III; Placebos - administration & dosage; Progression-Free Survival; Ramucirumab; Regional subset; Response Evaluation Criteria in Solid Tumors; Survival Rate; United States; Vascular endothelial growth factor; Young Adult; United States; Europe; Phase III; Ethnicity; Vascular endothelial growth factor; Regional subset; Epidermal growth factor receptor
• ISSN: 2468-2942; 2468-2942
• DOI: 10.1016/j.ctarc.2021.100378

•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. 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 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. 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%]). 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.