454P Efficacy of crizotinib in NSCLC with concomitant ALK fusion and c-MET overexpression

Abstract

Background ALK fusion is a common driver gene in non-small-cell lung cancer (NSCLC), accounting for 3%-13%. Crizotinb is considered as first-line therapy for advanced ALK-positive patients. Patients with c-MET overexpression obtained clinical benefit from crizotinib, with the frequency of 31.9%. We investigated the efficacy of crizotinb in patients with concomitant ALK fusion and c-MET overexpression. Methods We identified 203 ALK-positive advanced NSCLC patients from January 2010 to November 2015 with any of the 3 methods:FISH, RACE-PCR, or Ventana IHC. A total of 113 patients were under the analysis of c-MET overexpression by IHC, in which 50% tumor cells with moderate to high intensity staining were defined as c-MET positive. Patients with ALK and c-MET positive are considered as Group A, while others as Group B. Besides, we defined patients with c-MET of 50% tumor cells with high intensity staining and ALK fusion as Group C, while others as Group D. All patients were identified without EGFR mutation by DNA direct sequencing or Scorpion amplification refractory mutation system. Results Among ALK-positive NSCLC patients, the frequency of c-MET positive was 29.2% (33/113). A total of 22 patients with concomitant ALK fusion and c-MET overexpression and 54 patients with only ALK fusion received crizotinib in their first- or further-line settings. There was no significant difference in age (P = 0.629), gender (P = 0.659), smoking history (P = 0.745), and histology (P = 0.498) between these two arms.Objective response rate (ORR) of crizotinib was 72.7% (16/22) in Group A and 63.0% (34/54) in Group B (P = 0.416). Median PFS of crizotinib was 12.8 vs 9.5 months in these two groups (P = 0.514).Median OS was 33.0 vs 29.5 months, with Hazard ratio (HR) of 1.038(P = 0.919). Eight patients were identified in group C with ORR of 100.0% (8/8), higher than those in group D (P = 0.046). Median PFS was 16.8 vs 9.3 months in these two groups, with HR of 0.548 (P = 0.079). Median OS was 34.0 vs 29.5 months, with HR of 0.633 (P = 0.347). Conclusions Similar efficacy with crizotinib was obtained in ALK-positive patients with or without c-MET overexpression. However, there was a trend of better efficacy with crizotinib in ALK-rearranged patients with more than 50% tumor cells of strong c- MET overexpression. Legal entity responsible for the study: Guangdong Lung Cancer Institute Funding Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China Disclosure All authors have declared no conflicts of interest.