Tyrosine-Kinase Inhibitors for Lung or Breast Cancer and Drug-Drug-interactions: a clinical guide

Fiorenza Santamaria^1*Michela Roberto²Giulia Maltese³Francesco Nicolella³Andrea Torchia³Dorelsa Buccilli³Mattia Alberto Di Civita¹Paola Giancontieri³Daniele Marinelli¹Alessio Cirillo³Vincenzo Bianco²Monica Verrico²ANDREA Botticelli³Daniele Santini³

• ¹Department of Experimental Medicine, Faculty of Medicine and Dentistry, Sapienza University of Rome, Rome, Lazio, Italy
• ²Umberto 1 Hospital, Rome, Sicily, Italy
• ³Sapienza University of Rome, Rome, Lazio, Italy

Introduction: In the last two decades, Tyrosine-kinase inhibitors (TKIs) have dramatically changed prognosis among Lung and Breast Cancers, with a significant benefit in metastatic and, more recently, in the adjuvant setting in selected groups of patients. Despite their favorable oncological action, TKIs are at high risk for Drug-Drug-Interactions (DDIs) due to their pharmacokinetic (PK) depending both on pH-dependent absorption and on liver metabolism. However, the DDIs are frequently related to “potential DDI” (pDDI) and their relevance in clinical practice often underestimated and there is a lack of practical guide for clinicians. Methods and Materials: We conducted a narrative review restricted to the last twenty years, to adults (aged 18 years or older) with lung or breast cancers treated with TKIs and clinical data of potential DDIs and with reported toxicities or outcome. Results: We summarized the pharmacokinetic profile and the clinical evidence of eleven TKIs used for Lung or Breast Cancers. Moreover, we provided an easy-to-use guide to help physicians in clinical practice with recommended dose adjustment or cautions required for preventing severe adverse events or possible change in TKIs availability in presence of other interfering drugs. Conclusions: The level of evidence for DDIs during TKI treatment is low because most available data are from phase I studies in healthy volunteers and few phase II studies in cancer patients. However, since the occurrence of DDIs could be clinically significant as well as a prompt drug reconciliation process useful to prevent it, further, prospective, large sample size clinical trials should be carried out.