6533b86efe1ef96bd12cac0b

RESEARCH PRODUCT

Management of toxicities associated with targeted therapies for HR-positive metastatic breast cancer: a multidisciplinary approach is the key to success

Cazzaniga M. E.Danesi R.Girmenia C.Invernizzi P.Elvevi A.Uguccioni M.Amaducci L.Atzori F.Blasi L.Butti C.Collova E.De Conciliis E.Fabi A.Febbraro A.Garrone O.Gianni L.Giotta F.La Verde N.Michelotti A.Palumbo R.Paris I.Pistelli M.Pizzuti L.Rubino D.Valerio M. R.Zustovich F.

subject

0301 basic medicineCancer ResearchReviewDiseasechemistry.chemical_compound0302 clinical medicineRibociclibMolecular Targeted TherapyAbemaciclibClinical Trials as TopicDisease ManagementMetastatic breast cancerEverolimuOncologyReceptors Estrogen030220 oncology & carcinogenesisFemaleAdvanced breast cancerReceptors ProgesteroneBreast Neoplasmmedicine.drugHumanmedicine.medical_specialtyNeutropeniaDrug-Related Side Effects and Adverse ReactionsAntineoplastic Agents HormonalProtein Kinase InhibitorBreast NeoplasmsPalbociclibPalbociclib03 medical and health sciencesBreast cancermedicineBiomarkers TumorHumansEverolimusIntensive care medicineAdverse effectProtein Kinase InhibitorsEverolimusbusiness.industrymedicine.diseaseClinical trialAbemaciclib030104 developmental biologychemistryMED/06 - ONCOLOGIA MEDICAbusinessDrug-Related Side Effects and Adverse ReactionAbemaciclib; Advanced breast cancer; Everolimus; Neutropenia; Palbociclib; Ribociclib

description

Purpose: Agents targeting HR-positive, HER2-negative locally advanced or metastatic breast cancer have improved patient outcomes compared with conventional single-agent endocrine therapy. Currently, approved targeted agents include everolimus and three CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib. Unlike the well-characterized and easily manageable safety profile of endocrine therapies, adverse events associated with targeted therapies are complex and potentially severe. Their prompt recognition and treatment, crucial for prolonged endocrine sensitivity and survival, may be challenging and requires a multidisciplinary effort and a good knowledge of drug interactions. Methods: We reviewed the current evidence on the drug safety of targeted agents for metastatic breast cancer currently used in clinical practice in Italy, supported by the clinical experience of Italian oncologists with expertise in the field. Results: All oncologists had used CDK4/6 inhibitors in clinical practice and/or within a clinical trial. The clinical management of toxicities, including dose adjustments, treatment interruptions, and concerns regarding special populations is discussed, and the management of relevant adverse events, related to individual agents and class-specific, toxicities is reviewed. Hematologic toxicities have the greatest impact on clinical management of the disease and on patients. Although toxicities associated with the new treatments result in more visits to the physician and more time and attention with patients, they are manageable, with no need for the oncologist to consult with specialist physicians. Conclusions: Based on the available evidence and current guidelines, we propose a series of practical recommendations for multidisciplinary clinical management of the various toxicities associated with the addition of targeted agents to endocrine therapy.

10.1007/s10549-019-05261-5http://hdl.handle.net/10447/359844