RAMOSE Study Results: Ramucirumab Combined With Osimertinib Shows Benefits in Patients With EGFR-Mutant Metastatic Lung Cancer

EGFR-mutated non-small cell lung cancer (NSCLC) represents one of the most aggressive forms of lung cancer. The RAMOSE study, a phase II clinical trial, investigated the combination of ramucirumab with osimertinib for patients with metastatic lung cancer not previously treated with EGFR-targeted tyrosine kinase inhibitors (TKI). The aim was to evaluate the efficacy and safety of this combination compared to osimertinib monotherapy.

The study methodology involved 159 patients randomly assigned to two groups: arm A received ramucirumab (10 mg/kg) intravenously every 3 weeks in combination with osimertinib (80 mg orally, once daily), and arm B received osimertinib alone. Patients were followed for a mean of 16.6 months. The analyses were performed based on response evaluation criteria (RECIST v1.1), evaluating disease progression and objective response rates (ORR), disease control (DCR), among others. In addition, safety was closely monitored, focusing on adverse events (AEs) and treatment discontinuation rates.

Preliminary results showed that the combination of ramucirumab with osimertinib (arm A) led to a significant increase in progression-free survival (PFS) compared to the monotherapy group (arm B). The median PFS was 24.8 months in arm A, versus 15.6 months in arm B (HR 0.55, P=0.023). The one-year PFS rate was 77% in arm A, versus 62% in arm B. The two-year PFS rate was 51% for arm A and 30% for arm B. These differences indicate that the therapeutic combination may provide a clinically relevant advantage for these patients.

Regarding the subgroups analyzed, the benefit of PFS with the combination was consistent regardless of the EGFR mutation (exon 19 or L858R) or the presence of brain metastases. Among patients with brain metastases, group A also had better outcomes, with a median PFS of 17.9 months, versus 13.8 months in group B. For patients without brain metastases, the benefit was even more pronounced in arm A, with PFS not achieved, while arm B had 18.4 months of PFS.

In terms of safety, the combination of ramucirumab with osimertinib was well tolerated by patients, with a high rate of treatment adherence. Most of the adverse effects observed were grade 1 or 2, the most common being diarrhea, fatigue, and headache. Only 1 patient in arm A had grade 4 adverse effects (hyponatremia). Among the adverse effects of interest related to ramucirumab, hypertension, epistaxis and proteinuria stood out, which were closely monitored, but without new safety signals.

The results of the RAMOSE study indicate that the combination of ramucirumab with osimertinib presents a promising efficacy profile for patients with EGFR-mutant metastatic lung cancer, with clear benefits in terms of progression-free survival. The combination proved to be safe and well tolerated, with controllable adverse effects. The results reinforce the need for further research on new therapeutic approaches for this group of patients, aiming to further improve clinical outcomes and quality of life.