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Pralsetinib and Sequential MET Inhibitors to Overcome MET Amplification Resistance in a Patient With a RET Fusion Driven Lung Cancer – Case Report

Published:August 19, 2022DOI:https://doi.org/10.1016/j.cllc.2022.08.010

      Clinical Practice Points

      • What is already known about this subject?
      • Rearranged during transfection (RET) gene fusion are unfrequent (1%-2%) but validated as target mutations in non-small cell lung cancer (NSCLC).
      • Selpercatinib and, pralsetinib have been authorized by the US-FDA in second line or more in NSCLC RET+.
      • The predominant independent mechanism of resistance to RET tyrosine kinase inhibitors (TKI) is the MET amplification but data to overcome MET resistance concern only selpercatinib resistance.
      • What are the new findings and how might they impact on clinical practice in the foreseeable future?
      • We report here the first case of a patient who developed a MET amplification as an initial mechanism of acquired resistance to pralsetinib for an advanced KIF5B-RET driven lung adenocarcinoma, successfully treated with a combination of pralsetinib and crizotinib then capmatinib due to an isolated cerebral progression.
      • An isolated progression under crizotinib should raise suspicion of poor penetration through the blood-brain barrier and motivate the switch by an anti-MET with better cerebral penetration like capmatinib.
      • Early evaluation by 18FDG/CT might be a compelling method to justifying the pursuit or not of combination TKI without being predictive of the duration of response.

      Keywords

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