A large retrospective analysis of the activity of pemetrexed (PEM) in patients (pts) with ALK-positive (ALK+) non-small cell lung cancer (NSCLC) prior to crizotinib (CRIZ).

Abstract

7599 Background: Retrospective small cohort studies suggest ALK+ NSCLC may be particularly sensitive to PEM. Methods: PROFILE 1005 (NCT00932451; Pfizer) is a large phase 2 multi-center, single-arm study of CRIZ in previously treated ALK+ NSCLC. Eligibility criteria included pts with progressive disease from the PEM arm of companion trial PROFILE 1007. We retrospectively assessed objective response rate (ORR) and time to progression (TTP; 1st dose to objective progression) in pts who received PEM prior to CRIZ. ORR with CRIZ post-PEM was assessed. Results: Of the 439 ALK+ pts enrolled as of June 2011, 369 (84.1%) received prior PEM (single agent or combination; any line advanced/metastatic) with a cumulative ORR of 18.7%. In pts who received PEM combinations 1st-line (1L; n=120) or 2nd-line (2L; n=60), ORR was 24.2% and 16.7%; and median TTP was 6.9 months (mo; 95% CI: 6.0–7.4) and 6.9 mo (95% CI: 4.8–8.8), respectively. In pts who received 2L single-agent PEM (n=80), ORR was 12.5% and median TTP was 5.3 mo (95% CI: 3.0–6.6). In pts treated with PEM 3rd-line (3L) or later (n=138), ORR was 16.7%. By line of PEM treatment, ORR was lower and TTP shorter than that reported in small ALK+ cohorts evaluating multiple lines of treatment. In 2L, previously reported ORR and median PFS with single-agent PEM in adenocarcinoma NSCLC were 12.8% (n=158) and 3.5 mo (n=283), and comparable to our findings. Pts who received 2L single-agent PEM (n=80) subsequently achieved higher ORR with CRIZ (54%; 95% CI: 42–65). Similar analyses in the 1L and 3L groups are ongoing. Conclusions: This retrospective study in predominantly never-smokers with ALK+ NSCLC reports lower ORR and shorter TTP with PEM than that reported in smaller retrospective ALK+ NSCLC cohorts. This finding may be in part due to the inclusion of crossover pts from PROFILE 1007. This analysis and previous reports observed a tendency to a higher response rate and better PFS or TTP with PEM than in unselected populations in 2L, which may not be specifically related to ALK status but to a higher sensitivity to cytotoxic agents in never-smokers. Results from an ongoing phase 3 trial (PROFILE 1007) will provide additional information.