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Review
. 2019 Aug;176(3):483-494.
doi: 10.1007/s10549-019-05261-5. Epub 2019 May 7.

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

Marina Elena Cazzaniga  1 , Romano Danesi  2 , Corrado Girmenia  3 , Pietro Invernizzi  4 , Alessandra Elvevi  4 , Massimo Uguccioni  5 ; NetworkER+
Collaborators, Affiliations
Review

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

Marina Elena Cazzaniga et al. Breast Cancer Res Treat. 2019 Aug.

Abstract

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.

Keywords: Abemaciclib; Advanced breast cancer; Everolimus; Neutropenia; Palbociclib; Ribociclib.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Management of CDK4/6-related neutropenia as recommended in the labels of palbociclib, ribociclib, and abemaciclib. For the recommended dose adjustments, please refer to Table 2. ANC absolute neutrophil count, CBC complete blood count. *The label of abemaciclib does not differentiate between grade 3 neutropenia with or without fever > 38.5 °C and/or infection. Reproduced with permission from Spring et al. [17]
Fig. 2
Fig. 2
Assessment of patients at risk of QTc prolongation or with QTc prolongation before or during cancer treatment. Reproduced with permission from Porta-Sanchez et al. [40]
See this image and copyright information in PMC

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