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)

Author(s): Xiuning Le, MD, PhD¹;Jyoti D. Patel, MD²;Elaine Shum, MD³;Christina Baik, MD⁴;Rachel E. Sanborn, MD⁵;Catherine A. Shu, MD⁶;Chul Kim, MD⁷;Mary Jo Fidler, MD⁸;Richard Hall, MD⁹;Yasir Y. Elamin, MD¹;Janet Tu, MD¹;George Blumenschein, MD¹;Jianjun Zhang, MD, PhD¹;Don Gibbons, MD, PhD¹;Carl Gay, MD, PhD¹;Nisha A. Mohindra, MD²;Young Chae, MD²;Yanis Boumber, MD²;Joshua Sabari, MD³;Rafael Santana-Davila, MD⁴;Shane Rogosin, MD⁵;Benjamin Herzberg, MD⁶;Ben Creelan, MD¹⁰;Bruna Pellini, MD¹⁰;Tawee Tanvetyanon, MD¹⁰;Simon Heeke, PhD¹;Mike Hernandez, PhD¹;Jhanelle E. Gray, MD¹⁰;Andreas Saltos, MD¹⁰;John V. Heymach, MD, PhD¹;

Source: https://doi.org/10.1200/JCO.24.00533

Dr. Maen Hussein's Thoughts

Improved progression-free survival (PFS), now we have osimertinib and ramucirumab, amivantamab and Lazertinib (PFS 24.8 vs 23 months but NOT head to head).

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.

Author Affiliations

¹UT MD Anderson Cancer Center, Houston, TX;²Northwestern University, Chicago, IL;³New York University Cancer Center, New York, NY;⁴University of Washington, Seattle, WA;⁵Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR;⁶Columbia University Irving Medical Center, New York, NY;⁷Georgetown University, Washington, DC;⁸Rush University, Chicago, IL;⁹Virginia University, Charlottesville, VA;¹⁰Moffitt Cancer Center, Tampa, FL

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