(ChemotherapyAdvisor) – Adding ramucirumab to first-line platinum chemotherapy for non-small cell lung cancer (NSCLC) shows promising rates of progression-free survival (PFS) and tolerable toxicities, according to two Eli Lilly-funded Phase 2 studies presented at the European Society for Medical Oncology (ESMO) 2012 Congress in Vienna, Austria.
Interim analyses of PFS, tolerability, and safety supported further study of ramucirumab as a potential addition to first-line platinum-based chemotherapy and pemetrexed for patients with nonsquamous-cell NSCLC, the authors concluded.
“We are encouraged by these results from two Phase II trials indicating ramucirumab may be beneficial to patients with non-small cell lung cancer,” said Richard Gaynor, MD, vice president for product development and medical affairs at Lilly Oncology. “These findings support our ongoing evaluation of ramucirumab for lung cancer patients and will need to be confirmed in larger pivotal studies.”
The first study (ESMO Abstract #1245), a randomized open-label Phase 2 study of 140 chemotherapy-naive patients, assessed PFS among patients with advanced nonsquamous-cell NSCLC who received ramucirumab plus first-line chemotherapy.
Interim median PFS was 4.3 months for control-arm patients and 6.3 months for ramucirumab-arm patients (HR 0.48 [90% CI: 0.31-0.74]), the authors reported. Disease control rate (DCR) was 72% for control-arm patients and 87% for ramucirumab-arm patients, the authors reported.
Grade 3 and higher toxicities for patients receiving ramucirumab included thrombocytopenia (22% vs 19% of control-arm patients); neutropenia (18% vs 17%); fatigue (12% vs 17%); anemia (10% vs 16%); hypertension (10% vs 1%); and nausea (10% vs 7%).
The second study (ESMO Abstract #1287) was an open-label Phase 2 study of 40 patients with advanced NSCLC, who were administered ramucirumab (10 mg/kg) plus paclitaxel (200mg/m2) and carboplatin (AUC=6) for up to six 3-week cycles, followed by maintenance ramucirumab. Median PFS was 7.85 months. Overall DCR (CR+PR+SD) was 90%, and PFS at 6 months was 59.0% (95% CI: 41.3%-72.9%), the authors reported. As with the first study, the most common Grade 3+ toxicities associated with ramucirumab were neutropenia (13%), thromboycytopenia (10%), and fatigue (8%); in the second study, febrile neutropenia was seen in 8% of patients receiving ramucirumab.
Ramucirumab is a human IgG1 monoclonal antibody receptor antagonist that blocks VEGF-A, VEGF-C, and VEGF-D interactions and receptor activation – inhibiting endothelial cell proliferation, migration, and vascular permeability. Six Phase 3 trials are currently underway for ramucirumab, the authors noted.
Abstracts (#1245, #1287)