Results from the REVEL Trial: Exposure-Response Relationship for Ramucirumab plus Docetaxel vs Docetaxel as Second-line Treatment of Metastatic NSCLC
Ramucirumab (RAM) is a recombinant, fully human anti-VEGFR-2 monoclonal antibody that has been FDA approved as second line therapy with docetaxel in patients with metastatic NSCLC who have experienced disease progression during or after platinum-based chemotherapy. An exploratory exposure-response analysis for RAM was performed using data from the REVEL trial.a Such exposure-response analysis is increasingly recognized as necessary to optimize the benefits of small molecules and monoclonal antibodies for patients.b Patients received RAM (10 mg/kg) or placebo (PL) + DOC (75 mg/m2) every 3 weeks, and pharmacokinetic (PK) samples were collected; a population PK (PopPK) analysis was conducted. Population pharmacokinetics (PopPK) model-predicted RAM exposure parameters (Cmin,1, Cmin,ss, Cmax,ss, and Cave,ss) were used to evaluate the relationship between RAM exposure and measures of efficacy and safety. Analyses included 376 RAM+DOC patients and 366 PL+DOC patients. Similar trends were seen for all four exposure parameters. As RAM exposure increased, greater improvements were seen in overall survival (OS) and progression-free survival (PFS) (see Table). A statistically significant correlation was also seen for RAM exposure and grade ? 3 febrile neutropenia and hypertension. These results from the exposure-response analysis suggest improvements in efficacy and increased toxicity may occur with increasing RAM exposure. RAM at a dose of 10 mg/kg every 3 weeks in combination with DOC appears to be most appropriate for the second-line indication in terms of efficacy and safety and offers an optimal benefit-risk profile in patients with metastatic NSCLC.
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