Gastrointestinal adverse effects of cyclin-dependent kinase 4 and 6 inhibitors in breast cancer patients: a systematic review and meta-analysis

Shohdy, Kyrillus S.; Lasheen, Shaimaa; Kassem, Loay; Abdel‐Rahman, Omar

doi:10.1177/2042098617722516

Cited by 33 publications

(29 citation statements)

References 29 publications

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“…The incidence of all-grade gastrointestinal (GI) toxicities is higher in patients treated with abemaciclib than in patients given palbociclib or ribociclib, although high-grade (3-4) events are relatively uncommon (Table 2) [22]. GI adverse drug reactions are generally well controlled by standard antiemetic (e.g., metoclopramide, serotonin 5-HT3 antagonists), while the prophylactic administration of loperamide is recommended to prevent diarrhea in patient treated with abemaciclib [23].…”

Section: Safetymentioning

confidence: 99%

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Drug-drug interactions in breast cancer patients treated with CDK4/6 inhibitors

Fogli

Curigliano

et al. 2019

Cancer Treatment Reviews

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CDK4/6 inhibitors are a new class of anticancer drugs used for the treatment of women with hormone receptorpositive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. Polypharmacy is a well-known problem in advanced cancer causing potential drug-drug interactions (DDIs), which, in turn, may limit the therapeutic value of CDK4/6 inhibitors. Therefore, understanding the mechanisms underlying potential DDIs in patients taking CDK4/6 inhibitors may be useful in decision-making processes and represent an important step towards treatment personalization. The present review is aimed at describing the potential DDIs that might occur in breast cancer patients receiving CDK4/6 inhibitors based on direct evidence from the literature and mechanistic considerations tailored on specific class of drugs used in combination.

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Section: Safetymentioning

confidence: 99%

“…In MONARCH 1, only one patient discontinued the treatment due to QT prolongation. References:[22,23,26,44].…”

mentioning

confidence: 99%

Drug-drug interactions in breast cancer patients treated with CDK4/6 inhibitors

Fogli

Curigliano

et al. 2019

Cancer Treatment Reviews

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“…The clinical relevance of the off-target kinase inhibitory activity for each of these drugs has yet to be fully assessed (Chen et al 2016). The increased potency of abemaciclib toward CDK9 (reported in some, but not all studies) (Gong et al 2017) correlates with a gastrointestinal toxicity profile specifically in those patients (Shohdy et al 2017). Conversely, abemaciclib allows for continuous dosing, whereas palbociclib and ribociclib require a break in treatment of 1 week in four in order to allow for neutrophil recovery.…”

Section: Cdk4/6 Inhibitorsmentioning

confidence: 99%

Overcoming CDK4/6 inhibitor resistance in ER-positive breast cancer

Portman

Alexandrou

Carson

et al. 2019

Endocrine-Related Cancer

122

121

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Three inhibitors of CDK4/6 kinases were recently FDA approved for use in combination with endocrine therapy, and they significantly increase the progression-free survival of patients with advanced estrogen receptor-positive (ER+) breast cancer in the first-line treatment setting. As the new standard of care in some countries, there is the clinical emergence of patients with breast cancer that is both CDK4/6 inhibitor and endocrine therapy resistant. The strategies to combat these cancers with resistance to multiple treatments are not yet defined and represent the next major clinical challenge in ER+ breast cancer. In this review, we discuss how the molecular landscape of endocrine therapy resistance may affect the response to CDK4/6 inhibitors, and how this intersects with biomarkers of intrinsic insensitivity. We identify the handful of pre-clinical models of acquired resistance to CDK4/6 inhibitors and discuss whether the molecular changes in these models are likely to be relevant or modified in the context of endocrine therapy resistance. Finally, we consider the crucial question of how some of these changes are potentially amenable to therapy.

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“…Indeed, GI events including nausea, vomiting, and diarrhea are shared by most anticancer drugs. A meta-analysis of four studies with CDK4/6 inhibitors (palbociclib, ribociclib) was performed to assess the risk of GI toxicities associated with CDK4/6 inhibitors [32]. Adding CDK4/6 inhibitors to endocrine therapy was found to marginally increase the incidence of any-grade decreased appetite, nausea, vomiting, and diarrhea with no significant increase in the risk of high-grade GI toxicities compared with control.…”

Section: Methodsmentioning

confidence: 99%

“…With regards to palbociclib, rabeprazole (a proton pump inhibitor) decreases its serum concentration and H2-receptor antagonists or locally acting antacids should be used for the management of nausea. Dexamethasone and aprepitant may, respectively, decrease or increase serum levels of palbociclib; possible alternatives are metoclopramide and domperidone [32].…”

Section: Methodsmentioning

confidence: 99%

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

Cazzaniga¹,

Danesi²,

Girmenia

et al. 2019

Breast Cancer Res Treat

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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.

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Gastrointestinal adverse effects of cyclin-dependent kinase 4 and 6 inhibitors in breast cancer patients: a systematic review and meta-analysis

Cited by 33 publications

References 29 publications

Drug-drug interactions in breast cancer patients treated with CDK4/6 inhibitors

Drug-drug interactions in breast cancer patients treated with CDK4/6 inhibitors

Overcoming CDK4/6 inhibitor resistance in ER-positive breast cancer

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

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