A Hoosier Cancer Research Network (HCRN) study, HCRN-LUN18-335, led by Xiuning Le, MD, PhD, of the University of Texas MD Anderson Cancer Center, was published in the Journal of Clinical Oncology on October 8, 2024. The article is titled, “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).” Congratulations to all co-authors and study teams whose hard work led to this publication!

Abstract:

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).

The RAMOSE trial (ClinicalTrials.gov identifier: NCT03909334, HCRN LUN18-335) 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.

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.

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.

Read the full article.

Authors:

Xiuning Le (University of Texas MD Anderson Cancer Center), Jyoti D. Patel, (Northwestern University) Elaine Shum (New York University Cancer Center), Christina Baik (University of Washington), Rachel E. Sanborn (Earle A. Chiles Research Institute, Providence Cancer Institute), Catherine A. Shu (Columbia University Irving Medical Center), Chul Kim (Georgetown University), Mary Jo Fidler (Rush University), Richard Hall (Virginia University), Yasir Y. Elamin (University of Texas MD Anderson Cancer Center), Janet Tu (University of Texas MD Anderson Cancer Center), George Blumenschein (University of Texas MD Anderson Cancer Center), Jianjun Zhang (University of Texas MD Anderson Cancer Center), Don Gibbons (University of Texas MD Anderson Cancer Center), Carl Gay (University of Texas MD Anderson Cancer Center), Nisha A. Mohindra (Northwestern University), Young Chae (Northwestern University), Yanis Boumber (Northwestern University), Joshua Sabari (New York University Cancer Center), Rafael Santana-Davila (University of Washington), Shane Rogosin (Earle A. Chiles Research Institute, Providence Cancer Institute), Benjamin Herzberg (Columbia University Irving Medical Center), Ben Creelan (Moffitt Cancer Center), Bruna Pellini (Moffitt Cancer Center), Tawee Tanvetyanon (Moffitt Cancer Center), Simon Heeke (University of Texas MD Anderson Cancer Center), Mike Hernandez (University of Texas MD Anderson Cancer Center), Jhanelle E. Gray (Moffitt Cancer Center), Andreas Saltos (Moffitt Cancer Center), John V. Heymach (University of Texas MD Anderson Cancer Center)

About Hoosier Cancer Research Network:
Hoosier Cancer Research Network conducts innovative cancer clinical trials in collaboration with more than 100 academic and community clinical research sites across the United States. Our studies are designed by cancer researchers from our member institutions. The HCRN staff includes 55 team members who work together to support all aspects of the studies we manage, from the time we receive the initial concept from a researcher through the final publication of the study results. Currently, we are supporting more than 70 clinical trials across a wide range of cancer types. Over our 40-year history, more than 10,000 participants in have enrolled in our clinical trials, leading to important discoveries that help cancer patients live longer and better after their cancer diagnosis.