Targeted Therapies for Lung Cancer by Unknown

Author:Unknown
Language: eng
Format: epub
ISBN: 9783030178321
Publisher: Springer International Publishing

Crizotinib (PF-02341066)

Crizotinib is a small molecule inhibitor that competitively binds to the ATP-binding pocket of MET. Patients with MET amplification have shown remarkable response to this drug. Originally developed as a MET inhibitor, this compound also exhibited activity against anaplastic lymphoma kinase (ALK) [54] and ROS proto-oncogene 1 (ROS) rearrangements, leading to clinical trials targeting patients with this mutation. More recent studies have shown that patients with MET amplification and no ALK rearrangement treated with crizotinib have responded well in NSCLC [55] and squamous cell lung carcinoma [56]. We were the first to identify MET exon 14 skipping in patients and demonstrate that this variant can serve as a biomarker. Such biomarkers can aid clinical decisions by correctly identifying patients that would most likely benefit from MET-targeted therapies of differing class. Earlier this year, the US Food and Drug Administration (FDA) granted crizotinib a breakthrough therapy designation for the treatment of patients with metastatic NSCLC harboring MET exon 14 alterations that progress after receiving platinum-based chemotherapy. An expansion cohort of 21 patients from the PROFILE 1001 study with MET exon 14-altered NSCLC were treated with crizotinib 250 mg twice/day for 0.5–9.1+ months. Among 18 evaluable patients, 8 patients had partial responses and 9 patients had stable disease. None had progressive disease. Most adverse events were grade 1 and 2 with one case of grade 3 edema and one case of grade 3 bradycardia. No grade 4 adverse events occurred [57]. This significant designation underscores the urgency for identifying additional biomarkers and our commitment to delivering personalized medicine for patients that carry these genomic alterations.

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