The Combined Therapy of Cabozantinib, Crizotinib, and Osimertinib in a Lung Cancer Patient with Acquired MET Amplification and Resistance Mutations

Author:

Jóri Balázs12ORCID,Vössing Christine12,Pirngruber Judith12,Willing Eva Maria12ORCID,Arndt Kathrin12,Falk Markus12ORCID,Tiemann Markus2,Heukamp Lukas C.12,Hoffknecht Petra13

Affiliation:

1. Lungenkrebsmedizin Oldenburg, Georgstraße 12, 26121 Oldenburg, Germany

2. Institut für Hämatopathologie Hamburg, Fangdieckstraße 75A, 22547 Hamburg, Germany

3. Department of Thorax Oncology, Niels-Stensen-Kliniken, Franziskus-Hospital Harderberg Alte, Rothen-Felder Straße 23, 49124 Georgsmarienhütte, Germany

Abstract

EGFR-mutant lung cancers develop a wide range of potential resistance alterations under therapy with the third-generation EGFR tyrosine kinase inhibitor osimertinib. MET amplification ranks among the most common acquired resistance alterations and is currently being investigated as a therapeutic target in several studies. Nevertheless, targeted therapy of MET might similarly result in acquired resistance by point mutations in MET, which further expands therapeutic and diagnostic challenges. Here, we report a 50-year-old male patient with EGFR-mutant lung adenocarcinoma and stepwise acquired resistance by a focal amplification of MET followed by D1246N (D1228N), D1246H (D1228H), and L1213V (L1195V) point mutations in MET, all detected by NGS. The patient successfully responded to the combined and sequential treatment of osimertinib, osimertinib/crizotinib, and third-line osimertinib/cabozantinib. This case highlights the importance of well-designed, sequential molecular diagnostic analyses and the personalized treatment of patients with acquired resistance.

Publisher

MDPI AG

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