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

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

doi:10.1007/s12282-017-0818-4

Cited by 38 publications

(33 citation statements)

References 24 publications

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“…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. All three inhibitors are associated with toxicities resulting in loss of haematocytes (Kassem et al 2018), consistent with a role for CDK6 in the activation of haematopoetic stem cells (Scheicher et al 2015). Toxicities associated with all three drugs are, however, considered to be manageable and reversible (Spring et al 2017).…”

Section: Cdk4/6 Inhibitorsmentioning

confidence: 74%

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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Section: Cdk4/6 Inhibitorsmentioning

confidence: 74%

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

Portman

Alexandrou

Carson

et al. 2019

Endocrine-Related Cancer

122

121

View full text Add to dashboard Cite

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“…CDK4/6 inhibitors induce hematological adverse events ( Table 2). In particular, neutropenia represents the main dose-limiting toxicity for this class of drugs and it is most frequently observed in patients treated with palbociclib or ribociclib [19]. Neutropenia induced by CDK4/6 inhibitors is dose-dependent, rapidly reversible, usually not associated with febrile neutropenia, and manageable by dose delay or reduction [19].…”

Section: Safetymentioning

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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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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“…APL occurring after cancer treatments is a rare event representing approximately 11% of new APL patients [26]. We have found no evidence indicating that ALP might be complication of ribociclib or any other cdk 4/6 inhibitor [25,27]. Therapy-related APL may be associated with previous radiation or cytotoxic therapy, particularly topoisomerase II inhibitors.…”

Section: Discussionmentioning

confidence: 75%