TY - JOUR
T1 - 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)
AU - Le, Xiuning
AU - Patel, Jyoti D.
AU - Shum, Elaine
AU - Baik, Christina
AU - Sanborn, Rachel E.
AU - Shu, Catherine A.
AU - Kim, Chul
AU - Fidler, Mary Jo
AU - Hall, Richard
AU - Elamin, Yasir Y.
AU - Tu, Janet
AU - Blumenschein, George
AU - Zhang, Jianjun
AU - Gibbons, Don
AU - Gay, Carl
AU - Mohindra, Nisha A.
AU - Chae, Young
AU - Boumber, Yanis
AU - Sabari, Joshua
AU - Santana-Davila, Rafael
AU - Rogosin, Shane
AU - Herzberg, Benjamin
AU - Creelan, Ben
AU - Pellini, Bruna
AU - Tanvetyanon, Tawee
AU - Heeke, Simon
AU - Hernandez, Mike
AU - Gray, Jhanelle E.
AU - Saltos, Andreas
AU - Heymach, John V.
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2025/2/1
Y1 - 2025/2/1
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.24.00533
DO - 10.1200/JCO.24.00533
M3 - Article
C2 - 39378386
AN - SCOPUS:85206929041
SN - 0732-183X
VL - 43
SP - 403
EP - 411
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 4
ER -
