A Multicenter Open-Label Randomized Phase II Study of Osimertinib With and Without Ramucirumab in Tyrosine Kinase Inhibitor–Naïve Egfr-Mutant Metastatic Non–Small Cell Lung Cancer (Ramose Trial)

Authors

Xiuning Le
Jyoti D Patel
Elaine Shum
Christina Baik
Rachel E Sanborn
Catherine A Shu
Chul Kim
Mary Jo Fidler
Richard Hall
Yasir Y Elamin
Janet Tu
George Blumenschein
Jianjun Zhang
Don Gibbons
Carl Gay
Nisha A Mohindra
Young Chae
Yanis Boumber
Joshua Sabari
Rafael Santana-Davila
Shane Rogosin
Benjamin Herzberg
Ben Creelan
Bruna Pellini
Tawee Tanvetyanon
Simon Heeke
Mike Hernandez
Jhanelle E Gray
Andreas Saltos
John V Heymach

Publication Date

2-1-2025

Journal

Journal of Clinical Oncology

Abstract

Purpose: Preclinical studies demonstrated that dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways delay the emergence of resistance to EGFR tyrosine kinase inhibitors (TKIs), and in trials with first-generation EGFR TKIs, the combination of EGFR VEGF pathway inhibitors prolonged progression-free survival (PFS).

Methods: The RAMOSE trial (ClinicalTrials.gov identifier: NCT03909334, HCRN LUN-18-335) is a randomized, open-label multicenter phase II study comparing osimertinib with ramucirumab (arm A) to osimertinib (arm B) for initial treatment of metastatic EGFR-mutant non-small cell lung cancer (NSCLC) with 2:1 random assignment. The primary end point is PFS for evaluable patients; secondary end points include objective response rates (ORRs), disease control rate (DCR), overall survival, and safety. The stratification criteria were EGFR mutation type and the presence of CNS metastasis.

Results: At data cutoff on August 29, 2023, 160 patients consented, 147 patients received treatment, and 139 patients were evaluable with at least one scan. In this preplanned interim analysis, the median follow-up was 16.6 months. Among the evaluable patients, 57 PFS events occurred. The median PFS was 24.8 (A) versus 15.6 (B) months (hazard ratio, 0.55 [95% CI, 0.32 to 0.93]; log-rank P = .023), 12-month PFS rate was 76.7% (A) versus 61.9% (B; P = .026). No significant difference was observed in the ORRs and DCRs between arms. Any-grade (G) adverse events (AEs) occurred in 100% (A) and 98% (B) of patients, with no G5 treatment-related AE (TRAE), one G4 TRAE (hyponatremia, A), and 53% (A) versus 41% (B) G3 TRAEs. AE-related discontinuation occurred in 13 patients (9.7% in A and 8.7% in B). The safety profile was in line with known safety of each drug.

Conclusion: Ramucirumab plus osimertinib significantly prolonged PFS compared with osimertinib alone in patients with TKI-naïve EGFR-mutant NSCLC. The combination is safe and well tolerated.

Keywords

Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Acrylamides, ErbB Receptors, Aniline Compounds, Female, Male, Middle Aged, Ramucirumab, Aged, Antineoplastic Combined Chemotherapy Protocols, Mutation, Antibodies, Monoclonal, Humanized, Adult, Protein Kinase Inhibitors, Progression-Free Survival, Aged, 80 and over, Tyrosine Kinase Inhibitors, Indoles, Pyrimidines

DOI

10.1200/JCO.24.00533

PMID

39378386

PMCID

PMC11776886

PubMedCentral® Posted Date

10-8-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes