A combination of
tyrosine kinase inhibitors (TKIs) is likely to be a therapeutic option for numerous oncological situations due to high frequency of
oncogenic addiction and progress in precision oncology.
Non-small cell lung cancer (NSCLC) represents a subtype of
tumors for which oncogenic drivers are frequently involved. To the best of our knowledge, we report the first case of a patient treated with three different TKIs.
Osimertinib and
crizotinib were administered concurrently for an
epidermal growth factor receptor (EGFR)-mutated NSCLC developing a MET amplification as a resistance mechanism to
osimertinib. Simultaneously,
imatinib was administered for a metastatic
gastrointestinal stromal tumor. The progression-free survival was 7 months for both
tumors with this tritherapy. The use of therapeutic
drug monitoring to assess plasma concentrations of each TKI was a powerful tool to manage the toxicity profile of this combination (
creatine phosphokinase elevation) while preserving an optimal exposure to each TKI and treatment efficacy. We observed an
imatinib over-exposition related to
crizotinib introduction, probably explained by
drug-drug interaction mediated by
crizotinib enzymatic inhibition on
cytochrome P-450 3A4. Posology adjustment due to therapeutic
drug monitoring was probably involved in the good survival outcome of the patient. This tool should be used more routinely for patients treated by TKIs to prevent co-treatment interactions and, in particular, for patients receiving TKI combinations to obtain optimal therapeutic exposure and efficacy while reducing possible side-effects.