Clinical utility of ramucirumab in non-small-cell lung cancer

Lung cancer is the leading cause of cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases and approximately 70% of patients with NSCLC have locally advanced or metastatic disease at presentation. In NSCLC patients with advanced or metastatic disease, second line treatment with chemotherapy is associated with a poor response rate. In this article, we have reviewed the role of ramucirumab in patients with NSCLC. Ramucirumab is not current standard of care in the first line setting in the treatment of advanced or metastatic NSCLC, based on phase II data which did not show any progression-free survival (PFS) and overall survival (OS) benefit when ramucirumab was compared with non-ramucirumab arm. The REVEL study was a phase III, placebo-controlled trial which included patients with stage IV NSCLC who had progressed during or after platinum-based chemotherapy, with or without bevacizumab. Median OS was 9.1 months vs 10.5 months (HR 0.86, 95% CI 0.75-0.98) in the placebo and ramucirumab group respectively. Seventy-nine percent of patients in ramucirumab arm and 71% of patients in non-ramucirumab arm had grade ≥3 treatment-related adverse events. The addition of ramucirumab to docetaxel can be considered in younger patients with good performance status as a second line treatment option. Additionally, combined blockage of the VEGFR and EGFR pathway has been utilized to overcome resistance to EGFR therapy. The RELAY trial was a phase III, placebo-controlled trial which included patients with sensitizing EGFR mutation positive stage IV NSCLC. Patients were randomized to either ramucirumab plus erlotinib or erlotinib. The trial showed that the combination therapy showed superior PFS benefit.