Ramucirumab Added to Osimertinib Prolongs PFS for Patients With TKI-Naïve EGFR-Mutated Metastatic Non-Small Cell Lung Cancer

According to results from the phase 2 RAMOSE study, the addition of ramucirumab to osimertinib significantly prolonged survival for patients with tyrosine kinase inhibitor (TKI)-naive epidermal growth factor receptor (EGFR)-mutated metastatic non-small cell lung cancer (NSCLC). 

“As monotherapy, osimertinib provides a progression-free survival (PFS) of 18.9 months and overall survival (OS) of 38.6 months, with a well-tolerated toxicity profile…However, there is continued effort to improve upon the current clinical outcomes, including extending PFS,” stated Xiuning Le, MD, PhD, University of Texas MD Anderson Cancer Center, Houston, Texas, and coauthors. 

In this multicenter, open-label trial, 147 patients were randomized on a 2-to-1 basis to receive 80 mg of once daily osimertinib with (n = 105) or without (n = 54) 10 mg/kg of ramucirumab, administered once every 3 weeks. The primary end point was PFS. Key secondary end points included objective response rate (ORR), disease control rate, OS, and safety. 

At a median follow-up of 16.6 months, median PFS was 24.8 months in the ramucirumab arm and 15.6 months in the control arm (hazard ratio [HR], 0.55; 95% confidence interval [CI] 0.32 to 0.93; P = .023) and 12-month PFS rates were 76.7% and 61.9%, respectively (P = .026). The ORR was 76.3% in the ramucirumab arm and 80.4% in the control arm with disease control rates of 96.8% and 95.7%, respectively. OS data was immature at analysis. The most common grade ≥3 ramucirumab-related adverse events included hypertension, proteinuria, infusion-related reaction, diarrhea, fatigue, and anemia. 

“Results indicate that the addition of ramucirumab to osimertinib significantly prolongs PFS in TKI-naïve patients with NSCLC harboring EGFR classical mutations,” concluded Dr Le et al. “The combination demonstrated a safety profile in line with each drug without new safety signals, presenting a promising intensification strategy.” 

Journal of Clinical Oncology Associate Editor Thomas Stinchcombe, MD, Duke Cancer Institute, Durham, North Carolina, added, “The combination of osimertinib and ramucirumab is a potential treatment for patients with EGFR-mutant NSCLC.”

Source: 

Le X, Patel JD, Shum E, et al. 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). J Clin Oncol. Published online: October 8, 2024. doi: 10.1200/JCO.24.00533