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.
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