Multicenter randomized phase 2 trial of osimertinib with or without ramucirumab for TKI-naïve EGFR-mutant metastatic non-small cell lung cancer

Preclinical studies demonstrated that dual inhibition of EGFR and VEGF pathways delayed the emergence of resistance to EGFR TKIs. The multicenter randomized phase 2 RAMOSE trial evaluated osimertinib with or without ramucirumab for TKI-naïve EGFR-mutant metastatic non-small cell lung cancer (mNSCLC). Planned interim analysis of the trial found median progression-free survival of 24.8 months with osimertinib plus ramucirumab versus 15.6 months with osimertinib alone (HR 0.55; p=0.023) with 12-month PFS rate 76% versus 61,9%. There were no significant differences between the arms fot het endpoints objective response rate and disease controle rate. Any grade adverse events (AEs) occurred in 100% of patients with the combination and 98% of patients with osimertinib monotherapy. There were no grade 5 treatment-related AEs. AE-related discontinuations occurred in 9.7% of patients in the combination group and 8.7% of patients in the osimertinib monotherapy group. The authors conclude that ramucirumab plus osimertinib significantly prolonged PFS compared with osimertinib alone in patients with TKI-naïve EGFR-mutant mNSCLC.