Eli Lilly and Company announced it received approval from the US Food and Drug Administration (FDA) for the use of pemetrexed (Alimta), 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. Pemetrexed is not indicated for treatment of patients with squamous cell NSCLC.
This marks the third US indication for pemetrexed. In 2004, pemetrexed 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.
Phase III Trial
The current approval in first-line advanced NSCLC for nonsquamous cell histology is based on a phase III, open-label randomized study (1,725 patients) that evaluated pemetrexed plus cisplatin (AC arm) vs gemcitabine (Gemzar) 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). The median progression-free survival was 4.8 and 5.1 months for the AC and GC arms, respectively (adjusted hazard ratio = 1.04). The overall response rates were 27.1% and 24.7% for the AC and GC arms, respectively.
In a prespecified analysis, the impact of NSCLC histology on overall survival was examined. Clinically relevant differences in survival according to histology were observed. In the non–squamous cell NSCLC subgroup, the median survival was 11.0 and 10.1 months in the AC and GC groups, respectively. However, in the squamous cell histology subgroup, the median survival was 9.4 vs 10.8 months in the AC and GC groups, respectively. This unfavorable effect associated with squamous cell histology observed with pemetrexed was also noted in a retrospective analysis of the single-agent trial of pemetrexed vs docetaxel (Taxotere) in patients with stage III/IV NSCLC after prior chemotherapy.
Based on the same data, the FDA also approved a change to the second-line indication, ie, to patients with other than a predominantly squamous cell histology.