FDA Grants Eli Lilly and Company's ALIMTA(R) Third U.S. Approval
September 29, 2008
INDIANAPOLIS, Sept. 29 /PRNewswire-FirstCall/ -- Eli Lilly and Company (NYSE: LLY - News) announced today it received approval from the U.S. Food and Drug Administration (FDA) for the use of ALIMTA® (pemetrexed for injection), in combination with cisplatin, in the first-line treatment of locally-advanced and metastatic non-small cell lung cancer (NSCLC), for patients with nonsquamous histology. ALIMTA is not indicated for treatment of patients with squamous cell non-small cell lung cancer. NSCLC is the most common form of lung cancer, resulting in more than 180,000 new cases in the U.S. each year.(1,2)
NSCLC is defined as a group of histologies, that is, tumor types differentiated by cellular structure. Nonsquamous histology includes adenocarcinoma, large cell carcinoma and all other histologies except squamous cell carcinoma.
This marks the third U.S. indication for ALIMTA. In 2004, ALIMTA received consecutive approvals: first in combination with cisplatin as a treatment for patients with malignant pleural mesothelioma, whose disease is unresectable or who are otherwise not candidates for curative surgery, and then as a single agent for the second-line treatment of patients with locally-advanced or metastatic NSCLC after prior chemotherapy treatment.(3)
The ALIMTA approval in first-line advanced NSCLC for nonsquamous cell histology is based on a Phase III, open-label randomized study (1725 patients) that evaluated ALIMTA plus cisplatin (AC arm) versus GEMZAR® (gemcitabine HCl for injection) plus cisplatin (GC arm). The median survival was 10.3 months in the AC arm and 10.3 months in the GC arm [adjusted hazard ratio 0.94 (95% CI: 0.84, 1.05)]. The median progression-free survival was 4.8 and 5.1 months for the AC and GC arms, respectively [adjusted hazard ratio 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.
In a pre-specified analysis, the impact of NSCLC histology on overall survival was examined. Clinically relevant differences in survival according to histology were observed. In the nonsquamous cell NSCLC subgroup, the median survival was 11.0 and 10.1 months in the AC and GC groups, respectively [unadjusted hazard ratio 0.84 (95% CI: 0.74, 0.96)]. However, in the squamous cell histology subgroup, the median survival was 9.4 versus 10.8 months in the AC and GC groups, respectively [unadjusted hazard ratio 1.22 (95% CI: 0.99, 1.50)].(4) This unfavorable effect on overall survival associated with squamous cell histology observed with pemetrexed was also noted in a retrospective analysis of the single-agent trial of pemetrexed versus docetaxel in patients with stage III/IV NSCLC after prior chemotherapy.(5)
Patients treated with the ALIMTA regimen had less hematologic toxicity, fewer blood transfusions and decreased use of growth factors compared to those treated with the GEMZAR regimen. The most common adverse reactions (incidence greater than or equal to 20%) for ALIMTA in combination with cisplatin included vomiting, neutropenia, leukopenia, anemia, stomatitis/pharyngitis, thrombocytopenia and constipation.
Based on the same data, the FDA also approved a change to the second-line indication. ALIMTA is indicated as a single agent for the treatment of patients with locally-advanced or metastic nonsquamous non-small cell lung cancer after prior chemotherapy. ALIMTA is not indicated for treatment of patients with squamous cell non-small cell lung cancer.
For full prescribing and safety information about ALIMTA, visit www.ALIMTA.com.
Source: Eli Lilly and Company