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Master Thesis

Incidence et facteurs pronostiques des toxicités sévères des thérapies ciblées chez les patients âgés atteints de cancer

Abstract : Importance: the introduction of tyrosine and serine/threonine kinase inhibitors (TKI) has ushered in the era of personalized medicine in cancer therapy. Most of the data are extrapolated from larger trials in which older patients generally were a fraction of the participants. Therefore, safety data cannot be extrapolated to the general senior population. Objectives: to describe the incidence and prognostic factors of severe toxicities of TKI in cancer patients aged over 70 years. Design, settings and participants: the PreToxE study is an observational prospective/retrospective study. Patients ≥70 years-old with advanced solid tumor and treated with a TKI inhibitor as per drug label were enrolled. Main Outcome and measures: The primary endpoint is severe toxicity defined as treatment-related adverse death, persistent or significant disability/incapacity, hospitalization or discontinuation of treatment for more than three weeks. Results: 212 patients from two independent cohorts’ patients entered the study. Median age was 75 years-old (70-88). The most frequent solid tumors were lung (n=66, 31%), breast (n=52, 25%), soft tissues (n=30, 14%), kidney (n=13, 6%) and colon (n=10, 5%). The five most frequent prescribed TKIs were everolimus (n=52, 25%), erlotinib (n=44, 21%), pazopanib (n=39, 18%), regorafenib (n=20, 9%) and gefitinib (n=18, 9%). The prescribed dose was lower than that recommended in the drug label in 83 cases (39%). 87 (41%) patients had a severe toxicity as per protocol definition. This proportion was similar in an independent cohort including 99 patients (n=43, 43%). On multivariate analysis, polypharmacy was the sole factor associated with increased risk of severe toxicity. Conclusion and relevance: despite an upfront dose reduction in almost 50% of patients, severe toxicities occurred in about 40% of elderly patients treated with TKI. The use of at least three concomitant medications is highly predictive of severe toxicities.
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Submitted on : Wednesday, January 8, 2020 - 12:53:12 PM
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Coriolan Lebreton-Bourigault. Incidence et facteurs pronostiques des toxicités sévères des thérapies ciblées chez les patients âgés atteints de cancer. Sciences du Vivant [q-bio]. 2019. ⟨dumas-02432349⟩



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