title: Approval summary: pemetrexed in the initial treatment of advanced/metastatic non-small cell lung cancer.
abstract: On September 26, 2008, the U.S. Food and Drug Administration approved pemetrexed injection (Alimta Injection; Eli Lilly and Company, Indianapolis, IN) for use in combination with cisplatin for the initial treatment of patients with stage IIIB/IV nonsquamous non-small cell lung cancer (NSCLC). A randomized, phase III, open-label study was conducted in 1,725 patients. Patients were randomly assigned to receive 21-day cycles of pemetrexed plus cisplatin (AC) or gemcitabine plus cisplatin (GC). The primary objective was overall survival. The median survival time was 10.3 months in both the AC arm and the GC arm (adjusted hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.84-1.05). The median progression-free survival times were 4.8 and 5.1 months for the AC and GC arms, respectively (adjusted HR, 1.04; 95% CI, 0.94-1.15). The overall response rates were 27.1% and 24.7% for the AC and GC arms, respectively. A prespecified analysis of the impact of NSCLC histology on overall survival was conducted. In the nonsquamous NSCLC subgroup, the median survival times were 11.0 and 10.1 months in the AC and GC groups, respectively (unadjusted HR, 0.84; 95% CI, 0.74-0.96). However, in the squamous cell histology subgroup, the median survival times were 9.4 versus 10.8 months in the AC and GC groups, respectively (unadjusted HR, 1.22; 95% CI, 0.99-1.50). This unfavorable effect of squamous histology on overall survival was also noted in a retrospective analysis of a trial that compared pemetrexed with docetaxel in NSCLC patients who received prior chemotherapy. No new pemetrexed safety signals were observed.
authors.affiliation: Office of Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak Campus, Silver Spring, Maryland 20993-0002, USA. martin.cohen@fda.hhs.gov
authors.forename: Martin H
authors.initials: MH
authors.lastname: Cohen
authors.forename: Robert
authors.initials: R
authors.lastname: Justice
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D017277:Drug Approval; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D013997:Time Factors; D014481:United States; D014486:United States Food and Drug Administration; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D002945:Cisplatin; D000093542:Gemcitabine