Evaluation of Drug-Drug Interactions in EGFR-Mutated Non-Small-Cell Lung Cancer Patients during Treatment with Tyrosine-Kinase Inhibitors

Mario Occhipinti; Marta Brambilla; Giulia Galli; Sara Manglaviti; Maristella Giammaruco; Arsela Prelaj; Roberto Ferrara; Alessandro De Toma; Claudia Proto; Teresa Beninato; Emma Zattarin; Giuseppe Lo Russo; Alain Jonathan Gelibter; Maurizio Simmaco; Robert Preissner; Marina Chiara Garassino; Filippo De Braud; Paolo Marchetti

doi:10.3390/jpm11050424

Evaluation of Drug-Drug Interactions in EGFR-Mutated Non-Small-Cell Lung Cancer Patients during Treatment with Tyrosine-Kinase Inhibitors

J Pers Med. 2021 May 18;11(5):424. doi: 10.3390/jpm11050424.

Authors

Mario Occhipinti^{1

2}, Marta Brambilla¹, Giulia Galli¹, Sara Manglaviti¹, Maristella Giammaruco³, Arsela Prelaj^{1

4}, Roberto Ferrara¹, Alessandro De Toma¹, Claudia Proto¹, Teresa Beninato¹, Emma Zattarin¹, Giuseppe Lo Russo¹, Alain Jonathan Gelibter³, Maurizio Simmaco^{5

6}, Robert Preissner⁷, Marina Chiara Garassino^{1

8}, Filippo De Braud¹, Paolo Marchetti^{3

9}

Affiliations

¹ Thoracic Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, 20133 Milan, Italy.
² Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy.
³ Medical Oncology Unit B, Policlinico Umberto I, Sapienza University of Rome, Viale del Policlinico, 155, 00161 Roma, Italy.
⁴ Department of Electronics, Information, and Bioengineering, Politecnico di Milano, Via Giuseppe Ponzio, 34, 20133 Milano, Italy.
⁵ Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Sant'Andrea University Hospital, Via di Grottatossa, 1035, 00189 Rome, Italy.
⁶ Department of Advanced Molecular Diagnostics, Sapienza University of Rome, Sant'Andrea Hospital, Via di Grottatossa, 1035, 00189 Rome, Italy.
⁷ Institute of Physiology and Science-IT, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany.
⁸ Knapp Center for Biomedical Discovery, University of Chicago Medicine & Biological Sciences, 900 E 57th St, Chicago, IL 60637, USA.
⁹ Department of Clinical and Molecular Medicine, Sapienza University of Rome, Via di Grottarossa, 1035, 00189 Rome, Italy.

Abstract

(1) Background. The onset of a drug-drug interaction (DDI) may affect treatment efficacy and toxicity of advanced non-small-cell lung cancer (aNSCLC) patients during epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI) use. Here we present the use of Drug-PIN^® (Personalized Interactions Network) software to detect DDIs in aNSCLC patients undergoing EGFR-TKIs. (2) Methods. We enrolled patients with Stage IV aNSCLC already treated with or candidates to receive EGFR-TKIs, in any line; ECOG PS 0-2; taking at least one concomitant drug. Cancer treatments, concomitant drugs, and clinical and laboratory data were collected and inserted in Drug-PIN^®. (3) Results. Ninety-two patients, median age of 68.5 years (range 43-89), were included. In total, 20 clinically relevant DDIs needing medical intervention in a total of 14 patients were identified; the 14 major DDIs were related to a high-grade interaction between TKIs and SSRIs, antipsychotics, antiepileptics, H2-receptor antagonist and calcium antagonists. A negative association between statin intake and PFS was identified (p = 0.02; HR 0.281, 95% CI 0.096-0.825). (4) Conclusions. This is the first retrospective study assessing the prevalence of DDIs, the clinical need for medical intervention and the impact of concomitant drugs on EGFR-TKIs survival in aNSCLC.

Keywords: Drug-PIN®; EGFR; drug–drug interactions (DDI); non-small-cell lung cancer (NSCLC); tyrosine-kinase inhibitors (EGFR-TKIs).