On August 19, 2004, the FDA granted accelerated approval to pemetrexed for injection (Alimta®, made by Eli Lilly and Company) as a single agent for the treatment of patients with locally advanced or metastatic nonsmall cell lung cancer after prior chemotherapy.

Safety and efficacy were demonstrated in one multi-center, randomized trial in 571 patients comparing single-agent Alimta versus docetaxel. Alimta, 500 mg/m2 intravenously, was administered over 10 minutes on day 1 of each 21-day cycle. Patients receiving Alimta also received dexamethasone for skin rash prophylaxis and vitamin B12 and folic acid supplementation.

The primary efficacy endpoint was survival. Alimta failed to demonstrate superior survival compared to docetaxel. Non-inferiority for overall survival could not be demonstrated because there was only one small historical study (total 104 patients) from which to estimate docetaxel's survival effect. A meta-analysis of multiple historical studies is usually required for this survival effect estimation. In addition, comparison of the survival effect in the current randomized trial was confounded by a 32% crossover rate of Alimta patients to docetaxel after tumor progression. The median survival time was 8.3 months for Alimta-treated patients and 7.9 months for docetaxel-treated patients. Secondary efficacy endpoints included response rate (Alimta 9.1%, docetaxel 8.8%), progression-free survival (Alimta and docetaxel, medians 2.9 months) and time-to-progressive disease (Alimta, median 3.4 months; docetaxel, median 3.5 months).

Alimta has a more favorable safety profile than docetaxel. Alimta caused less neutropenia, febrile neutropenia, neutropenic infections and need for granulocyte/macrophage colony stimulating factors. Alimta causes less severe alopecia. Elevation of hepatic transaminases was more frequent with Alimta than docetaxel. Accelerated approval was based on the improved safety profile and effects on surrogate endpoints.

As a condition of accelerated approval, Eli Lilly and Company is required to conduct additional studies to demonstrate a clinical benefit, such as increased survival or improved disease-related symptoms.

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.

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