Activity of Crizotinib (PF02341066), a Dual Mesenchymal-Epithelial Transition (MET) and Anaplastic Lymphoma Kinase (ALK) Inhibitor, in a Non-small Cell Lung Cancer Patient with De Novo MET Amplification

Abstract

Crizotinib is a dual MET and ALK inhibitor. Currently, clinical development of crizotinib is focused primarily on ALK rearranged non-small cell lung cancer (NSCLC). Here we report an NSCLC patient with de novo MET amplification but no ALK rearrangement who achieved a rapid and durable response to crizotinib indicating is also a bona fide MET inhibitor.

ALK alterations in adult renal cell carcinoma: frequency, clinicopathologic features and outcome in a large series of consecutively treated patients

“…[15][16][17] Therefore, the identification of ALK rearrangements in other tumor types has gained importance owing to the potential for a similar treatment response. 19 Rearrangement of ALK has recently been reported in pediatric RCC.…”

“…Recently, the ALK inhibitor crizotinib was shown to be an effective therapy in patients with ALK-rearranged non-small cell lung cancers. [15][16][17] The present study involved screening RCCs from a large cohort of surgically treated adult patients from a single institution for ALK alterations. The goal was to define the frequency of ALK alterations, including rearrangements and copy number gain, in a comprehensive manner.…”

Anti-MET Targeted Therapy Has Come of Age: The First Durable Complete Response with MetMAb in Metastatic Gastric Cancer

“…In a recent case report authors described a NSCLC patient with de novo MET amplification, but without ALK rearrangement, who achieved a rapid and durable response to crizotinib, indicating it is also a bona-fide MET inhibitor (14). Dramatic clinical improvement and radiographic regression also were observed in patients with MET-amplified esophagogastric adenocarcinoma (15) and glioblastoma multiforme (16) upon treatment with crizotinib.…”

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

“…125,126,129 Regarding the significance of amplification alone, case reports have shown response to crizotinib. 134,135 The same challenges defining a clinically valid cutoff of MET amplification positivity exist in the setting of acquired resistance to EGFR TKI. A recent phase II study showed 40% response rate in patients with acquired EGFR TKI resistance and a MET copy number of 5 or higher when treated with a combination of gefitinib and capmatinib; no response was observed in a group with a MET copy number <5.…”