MET kinase mutations in lung cancer patients
| Autor: | Louise Kalmuk, Clotilde Descarpentries, Celine Mascaux, Camille Munck, Zoulika Kherrouche, Eric Wasielewski, Lucie Ulmer, Olivier Farchi, Fabienne Escande, Michele Beau-Faller, Alexis B Cortot |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 40:e21014-e21014 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | e21014 Background: Although mutations in the kinase domain of MET are well described in papillary renal cell carcinoma, they are rare and poorly studied in lung cancer, but could constitute a new therapeutic target given the availability of potent MET inhibitors. The characteristics of patients with MET kinase mutation in lung cancer are still unknown. Our objective was to describe the demographic, clinical and biological characteristics of these patients, and analyze their survival. Methods: We conducted a multicenter retrospective study including patients with lung cancer harboring a MET kinase mutation. Patients who had already received treatment with a MET TKI before the MET kinase mutation was found were excluded. Results: We identified 37 patients with a MET kinase mutation. Among them, 2 had already received a MET inhibitor and in 8 cases, the data were not accessible. A total of 27 patients were included in the final analysis, including 17 males (63%) and only 2 (8%) never smokers. The median age was 64 (range 43-86). Most patients had adenocarcinoma (n = 25, 93%). 19 patients were diagnosed at an advanced stage. The main metastatic sites were brain (n = 8, 42%), bones (n = 7, 37%) and lungs (n = 5, 19%). PDL1 expression level was available for 21 patients, and was < 1%, 1-49% and ≥50% in 4 (19%), 5 (24%) and 12 (57%) patients respectively. MET kinase mutations involved exon 15, 16, 17, 18 or 19 in 6 (22%), 7 (26%), 7 (26%), 3 (11%) and 4 (15%) patients respectively. The 2 most common mutations were H1112Y (4 patients) and H1097R (3 patients). 18 patients (67%) had a concurrent alteration by NGS including TP53 mutations (n = 11, 41%), KRAS mutations (n = 6, 22%) and NRAS mutations (n = 3, 11%). Overall, co-alterations involving known driver oncogenes were detected in 13 patients (48%). 19 patients received a first-line systemic treatment for advanced disease. Median progression-free survival with chemotherapy and immunotherapy was 10.5 and 6.4 months, respectively (p = 0.55). Median overall survival was 12.2 months. No patient received a MET inhibitor. Conclusions: MET kinase mutations are not associated with specific clinical characteristics and frequently occur together with other oncogene mutations. These results suggest that these mutations may not be sufficient to drive carcinogenesis by themselves. |
| Databáze: | OpenAIRE |
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