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 patients with progressive disease from the PEM arm of companion trial PROFILE 1007. We retrospectively assessed objective response rate (ORR) and time to progression (TTP; first dose to objective progression) in patients who received PEM before CRIZ. ORR with CRIZ post-PEM was assessed.Results
Of the 439 ALK+ patients 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 patients who received PEM combinations first-line (1L; n = 120) or second-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 patients 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 patients treated with PEM third-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. Patients 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 patients 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 the 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.