Alimta (Pemetrexed) as a Treatment for Nonsquamous, Nonsmall-Cell Lung Cancer

• Activity Number: 9
• Type: Invited
• Date/Time: Sunday, July 29, 2012 : 2:00 PM to 3:50 PM
• Sponsor: JSM 2012 Host Local Chapter - San Diego
• Author(s): Patrick M Peterson*+
• Companies: Eli Lilly and Company
• Keywords: interaction ; targeted ; histology ; pemetrexed ; Alimta ; NSCLC

Abstract

In 2007, results of a large randomized trial of patients with advanced non-small-cell lung cancer (NSCLC) confirmed a treatment-by-histology interaction effect that had previously been observed retrospectively in an earlier trial of pre-treated advanced NSCLC. Overall survival results in both trials showed that Alimta was effective in patients with non-squamous histology, with substantially reduced efficacy in patients with squamous histology. This effect was further confirmed by additional clinical trial results since 2007. Given the consistency across multiple trials, regulatory agencies worldwide have approved Alimta as a treatment for NSCLC only in patients with non-squamous histology. This presentation will review clinical and statistical evidence supporting Alimta as a "targeted" therapy for non-squamous NSCLC. Since studies have shown that Alimta inhibits thymidylate synthase (TS) in vitro, further discussion will consider the hypothesis that TS (over-expressed in squamous cell tumors) may provide a biological clue as to the reason for the observed interaction with histology. The role of histology generally as a cofactor for NSCLC will be examined and discussed.