A number of new antiangiogenic agents are in development for NSCLC. One of these, called motesanib, was tested in a randomized phase 3 trial called MONET1.⁸ Although this agent did not improve overall survival compared with placebo, there was an improvement in PFS and overall response. Another investigational agent, called aflibercept (VEGF Trap), acts as a decoy receptor for VEGF. By attaching itself to VEGF, aflibercept prevents the protein from binding to receptors on blood vessel cells and stimulating angiogenesis.⁹ Aflibercept is being evaluated in a phase 3 clinical study in combination with chemotherapy in NSCLC patients who have relapsed or had their cancer progress on front-line chemotherapy.¹⁰

Two of the newer investigational antiangiogenic agents for advanced NSCLC are ramucirumab (IMC-1121B), an antibody therapy against VEGF-receptor-2, and BIBF 1120, an orally administered angiogenesis inhibitor. Preliminary results from a phase 2 study of ramucirumab showed that 10 of 15 lung cancer patients (67%) who received this drug had their tumors shrink.¹¹ A phase 3 trial of ramucirumab in advanced NSCLC is enrolling patients.¹² In this trial, NSCLC patients will be randomly assigned to treatment with the chemotherapy drug docetaxel, either with or without ramucirumab. BIBF 1120 is being evaluated in two phase 3 clinical trials in advanced NSCLC, one trial in combination with docetaxel and the second in combination with pemtrexed.¹³ Both studies are in patients who have relapsed or progressed on front-line therapy.