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Regulatory Issues: FDA

Approval Summary: Pemetrexed in the Initial Treatment of Advanced/Metastatic Non-Small Cell Lung Cancer

Office of Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA

Key Words. Pemetrexed • Non-small cell lung cancer • First-line treatment

Correspondence: Martin H. Cohen, M.D., U.S. Food and Drug Administration, White Oak Campus, 10903 New Hampshire Avenue, Building 22, Room 2102, Silver Spring, Maryland 20993-0002, USA. Telephone: 301-796-1344; Fax: 301-796-9845; e-mail: martin.cohen{at}fda.hhs.gov

Received May 5, 2009; accepted for publication August 17, 2009; first published online in THE ONCOLOGIST Express on September 8, 2009.

Disclosures: Martin H. Cohen: None; Robert Justice: None; Richard Pazdur: None.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors or independent peer reviewers.

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.