title: Approval summary: pemetrexed maintenance therapy of advanced/metastatic nonsquamous, non-small cell lung cancer (NSCLC).
abstract: On July 2, 2009, the U.S. Food and Drug Administration approved pemetrexed injection (Alimta® Injection; Eli Lilly and Company, Indianapolis, IN) for maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based doublet induction chemotherapy. A double-blind study of pemetrexed plus best supportive care versus placebo plus best supportive care was conducted. Pemetrexed, 500 mg/m(2) i.v., was administered every 21 days until disease progression. Folic acid, vitamin B(12), and a corticosteroid were given to all study patients. There were 663 randomized patients (pemetrexed, 441; placebo, 222). Treatments were well balanced with respect to baseline disease characteristics and stratification factors. The median overall survival (OS) time for intent-to-treat (ITT) patients was 13.4 months for patients receiving pemetrexed and 10.6 months for those receiving placebo (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.65-0.95; p = .012). Median OS times were 15.5 months versus 10.3 months for patients with nonsquamous histologies receiving pemetrexed and placebo, respectively (HR, 0.70; 95% CI, 0.56-0.88). The median OS time in patients with squamous histology receiving pemetrexed was 9.9 months, versus 10.8 months for those receiving placebo (HR, 1.07; 95% CI, 0.77-1.50). A significantly longer progression-free survival interval for both the ITT and nonsquamous patient populations receiving pemetrexed maintenance therapy was also observed. The most common (>5%) adverse reactions in patients receiving pemetrexed were hematologic toxicity, an increase in hepatic enzymes, fatigue, gastrointestinal toxicity, sensory neuropathy, and skin rash.
authors.affiliation: Office of Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993-0002, USA. martin.cohen@fda.hhs.gov
authors.forename: Martin H
authors.initials: MH
authors.lastname: Cohen
authors.forename: Patricia
authors.initials: P
authors.lastname: Cortazar
authors.forename: Robert
authors.initials: R
authors.lastname: Justice
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy / Q000473:pathology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D004311:Double-Blind Method; D017277:Drug Approval; D005260:Female; D005971:Glutamates / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D010919:Placebos; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D010919:Placebos; D000068437:Pemetrexed; D006147:Guanine; D013940:Thymidylate Synthase