Abstract
ObjectivesTo describe characteristics, treatment and outcomes of non-small cell lung cancer (NSCLC) patients with MET alterations (MET exon 14 [METex14] skipping or MET amplification [METamp]) in real-world clinical care. MethodsThis non-interventional cohort study used real-world data extracted from electronic medical records from academic oncology sites in Israel, The Netherlands, Taiwan, and the USA. Patients had confirmed diagnosis of advanced (Stage IIIB–IV) NSCLC harboring MET alterations (date of diagnosis = index date) between 1 Jan 2010 and 30 Sept 2018. Medical history was assessed prior to and at the index date (baseline period), and outcomes from first date of treatment to death, loss to follow-up, or end of study period. ResultsA total of 117 patients were included (METex14 n = 70; METamp n = 47); testing methods were heterogeneous. Concomitant oncogenic mutations were more common in the METamp cohort than METex14. Patients in the METex14 cohort were older than those in METamp, and a larger proportion were never smokers. Anticancer first-line therapies received by patients (METex14; METamp) included chemotherapy only (44%; 41%), MET inhibitors (33%; 29%), immune checkpoint inhibitor (ICI) mono-(12%; 15%) and combination-therapy (8%; 3%). Second-line therapies included chemotherapy (35%; 30%) and MET inhibitors (30%; 39%). In the METex14 cohort, objective response rate (ORR) was generally low (first-line 28%; second-line 30%); no patients who received ICIs had a response. In the METamp cohort, ORR was 36% in first-line and 22% in second-line. Median (95% confidence interval) overall survival from start of first-line therapy was 12.0 months (6.8, 19.2) in the METex14 cohort and 22.0 months (9.8, 31.2) in METamp. ConclusionsHeterogeneous treatments reflect the changing landscape and availability of new treatments, as well as the high unmet medical need in older, METex14 patients who had more advanced disease at diagnosis. MET-targeted therapies could be beneficial in patients with these rare MET alterations.
Highlights
The receptor for hepatocyte growth factor (HGF), a tyrosine kinase that is encoded by the mesenchymal epithelial transition factor (MET) oncogene, has a crucial role in cancer growth, invasion and metastasis
METtargeted therapies could be beneficial in patients with these rare MET alterations
Oncogenic MET alterations can act as a primary driver of tumorigenesis, with tumor dependence on MET signaling for cancer initiation and progression, a phenomenon that is called ‘oncogene addiction’
Summary
The receptor for hepatocyte growth factor (HGF), a tyrosine kinase that is encoded by the mesenchymal epithelial transition factor (MET) oncogene, has a crucial role in cancer growth, invasion and metastasis. Oncogenic MET alterations can act as a primary driver of tumorigenesis, with tumor dependence on MET signaling for cancer initiation and progression, a phenomenon that is called ‘oncogene addiction’. MET exon 14 (METex14) skipping alterations and MET amplification have been identified as alterations that can convert MET into a primary oncogenic driver [1]. METex skipping alterations and MET amplification occur in a subset of treatment-naïve patients with non-small cell lung cancer (NSCLC) [1,2,3]. NSCLC harboring METex skipping alterations in about 8–15% harbor concomitant MET amplifications [4]; MET amplifica tion as a primary driver occurs as a distinct oncogenic event in the absence of METex skipping. Among patients with advanced NSCLC, both oncogenic MET activation as well as MET overexpression were shown to predict shorter survival [1,7]
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