Approval Summary: Pemetrexed Maintenance Therapy of Advanced/Metastatic Nonsquamous, Non‐Small Cell Lung Cancer (NSCLC)

• Published in: The oncologist (Dayton, Ohio) Ohio), 2010-12, Vol.15 (12), p.1352-1358
• Main Authors: Cohen, Martin H., Cortazar, Patricia, Justice, Robert, Pazdur, Richard
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Adenocarcinoma, Bronchiolo-Alveolar - drug therapy; Adenocarcinoma, Bronchiolo-Alveolar - pathology; Antineoplastic Agents - therapeutic use; Carcinoma, Large Cell - drug therapy; Carcinoma, Large Cell - pathology; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Double-Blind Method; Drug Approval; Female; Glutamates - therapeutic use; Guanine - analogs & derivatives; Guanine - therapeutic use; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Maintenance treatment; Male; Middle Aged; Neoplasm Staging; Non‐small cell lung cancer; Pemetrexed; Placebos; Regulatory Issues: FDA; Thymidylate Synthase - antagonists & inhibitors; Treatment Outcome; United States; United States Food and Drug Administration
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1634/theoncologist.2010-0224

Learning Objectives After completing this course, the reader will be able to: Consider tumor histology when making treatment decisions for patients with NSCLC. Identify patients with NSCLC who may be appropriate candidates for maintenance therapy with pemetrexed. This article is available for continuing medical education credit at CME.TheOncologist.com. 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/m2 i.v., was administered every 21 days until disease progression. Folic acid, vitamin B12, 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. The study that led to U.S. Food and Drug Administration approval of pemetrexed injection 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 is reviewed.