Clinical impact of drug-drug interactions on abemaciclib in the real-world experience of AB-ITALY study (vol 10, 58, 2024)

被引：0

作者：

Scagnoli, Simone

Pisegna, Simona

Toss, Angela

Caputo, Roberta

De Laurentiis, Michelino

Palleschi, Michela

de Giorgi, Ugo

Cortesi, Enrico

Fabbri, Agnese

Fabi, Alessandra

Paris, Ida

Orlandi, Armando

Curigliano, Giuseppe

Criscitiello, Carmen

Garrone, Ornella

Tomasello, Gianluca

D'Auria, Giuliana

Vici, Patrizia

Ricevuto, Enrico

Domati, Federica

Piombino, Claudia

Parola, Sara

Scafetta, Roberta

Cirillo, Alessio

Salimbeni, Beatrice Taurelli

Di Lisa, Francesca Sofia

Strigari, Lidia

Preissner, Robert

Simmaco, Maurizio

Santini, Daniele

Marchetti, Paolo

Botticelli, Andrea

机构：

[1] Department of Radiological, Oncological and Pathological Science, “Sapienza” University of Rome, Rome

[2] Department of Experimental Medicine, Sapienza University, Rome

[3] Department of Oncology and Hematology, Azienda Ospedaliero-Universitaria di Modena, Modena

[4] Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena

[5] Department of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Pascale, Naples

[6] IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” IRST Meldola IT, Meldola

[7] UOC Belcolle Hospital, Viterbo

[8] Precision Medicine in Senology, Department of Women Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome

[9] Precision Medicine in Senology, Scientific Directorate, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome

[10] Division of Gynecologic Oncology, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome

[11] Fondazione Policlinico Universitario Agostino Gemelli IRCCS Comprehensive Cancer Center, Unit of Medical Oncology, Rome

[12] Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan

[13] Department of Oncology and Hematology (DIPO), University of Milan, Milan

[14] Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, SC Oncologia Medica, Milan

[15] Sandro Pertini Hospital Unit of Medical Oncology, Rome

[16] Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale Tumori Regina Elena, UOSD Sperimentazioni di fase IV IT, Rome

[17] University of L’Aquila, L’Aquila

[18] Università Campus Biomedico, Rome

[19] IRCSS AOU Bologna, Bologna

[20] Institute of Physiology and Science-IT, Charité-Universitätsmedizin Berlin, Berlin

[21] Laboratory of Clinical Biochemistry, Sant’Andrea University Hospital, Rome

[22] Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, Rome

[23] Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome

[24] Medical Oncology A, AOU Policlinico Umberto I, Rome

[25] Istituto Dermopatico dell’Immacolata IRCCS, Rome

来源：

NPJ BREAST CANCER | 2024年 / 10卷 / 01期

关键词：

D O I：

10.1038/s41523-024-00682-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Abemaciclib demonstrated clinical benefit in women affected by HR+/HER2- advanced breast cancer (aBC). Drug-drug interactions (DDIs) can lead to reduced treatment efficacy or increased toxicity. This retro-prospective study aimed to evaluate outcomes, DDIs' impact, and toxicities of abemaciclib combined with endocrine therapy in a real-world setting. Patients from 12 referral Italian hospitals with HR+/HER2- aBC who received abemaciclib were included. Clinical data about comorbidities, concurrent medications, outcomes, and adverse events (AE) were collected. Drug-PIN (R) (Personalized Interactions Network) is a tool recognizing the role of multiple interactions between active and/or pro-drug forms combined with biochemical and demographic patient data. The software was used to define the Drug-PIN score and Drug-PIN tier (green, yellow, dark yellow, and red) for each patient. Univariate and multivariate analyses were performed to identify predictors of patients' PFS or toxicity. One hundred seventy-three patients were included. 13% of patients had >75years. The overall response rate (ORR) was 63%. The general population's median PFS (mPFS) was 22 months (mo), while mOS were not reached. Patients treated with abemaciclib in combination with AI and fulvestrant had a mPFS of 36 and 19 mo, respectively. The most common toxicities were diarrhea, asthenia, and neutropenia detected in 63%,49%, and 49% of patients. The number of concomitant medications and comorbidities were not associated with survival outcomes (22 vs 17 mo, p = 0.068, p = 0.99). Drug-PIN tier from dark yellow to red and Drug-PIN score >12 were associated with shorter PFS compared to no/low-risk DDIs and score <12 (15 vs 23, p = 0.005, p = 0.0017). Drug interaction was confirmed as an independent biomarker in a multivariate model (p = 0.02). No difference in any grade AE, severe toxicities, and diarrhea were detected among different age subgroups. No association was found between Drug-PIN score or Drug-PIN tier and overall toxicity (p = 0.44), severe AEs (p = 0.11), or drug reduction (p = 0.27). The efficacy and safety of abemaciclib plus ET were confirmed in a real-world setting, even in the elderly population and patients with comorbidities. Evaluation of DDIs with Drug-PIN appears to be an independent predictor of PFS.

引用

页数：1