CDK 4/6 inhibitors and stereotactic radiation in the management of hormone receptor positive breast cancer brain metastases

Figura, Nicholas; Potluri, T.; Mohammadi, Homan; Oliver, Daniel; Arrington, John A.; Robinson, Timothy J.; Etame, Arnold B.; Tran, Nam; Liu, James K.; Soliman, Hatem; Forsyth, Peter; Sahebjam, Solmaz; Yu, Hsiang‐Hsuan Michael; Han, Hyo S.; Ahmed, Kamran A.

doi:10.1007/s11060-019-03260-6

Cited by 54 publications

(38 citation statements)

References 42 publications

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“…Currently, there are six ongoing clinical trials (Table 3) as well as several small sample clinical studies (Table 4), which mostly target HR+/ HER2-metastatic breast cancer (MBC) patients. The preliminary results [83][84][85][86] propose that no significantly increased toxicity is observed, indicating that the combined therapy is promising as a novel strategy. Ippolito et al [84] reported that hematological toxicity neutropenia is most common among all adverse events.…”

Section: Clinical Studies Of Cdk4/6 Inhibitors In Combination With Ramentioning

confidence: 97%

“…In total, 60% of patients experienced grade 3 or greater neutropenia before combination treatment, suggesting that we should carefully evaluate previous toxicity to prevent reoccurrence. Figura et al [85] retrospectively analyzed 42 lesions in 15 brain MBC patients. Two lesions (5%) developed radiation necrosis, and both of them underwent four previous RT courses before the occurrence of radionecrosis, indicating the significance of cautious assessment of the treatment plan margins.…”

Section: Clinical Studies Of Cdk4/6 Inhibitors In Combination With Ramentioning

confidence: 99%

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CDK4/6 inhibitors: a novel strategy for tumor radiosensitization

Yang

Luo

Chen

et al. 2020

J Exp Clin Cancer Res

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Recently, the focus of enhancing tumor radiosensitivity has shifted from chemotherapeutics to targeted therapies. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are a novel class of selective cell cycle therapeutics that target the cyclin D-CDK4/6 complex and induce G1 phase arrest. These agents have demonstrated favorable effects when used as monotherapy or combined with endocrine therapy and targeted inhibitors, stimulating further explorations of other combination strategies. Multiple preclinical studies have indicated that CDK4/6 inhibitors exhibit a synergistic effect with radiotherapy both in vitro and in vivo. The principal mechanisms of radiosensitization effects include inhibition of DNA damage repair, enhancement of apoptosis, and blockade of cell cycle progression, which provide the rationale for clinical use. CDK4/6 inhibitors also induce cellular senescence and promote anti-tumor immunity, which might represent potential mechanisms for radiosensitization. Several small sample clinical studies have preliminarily indicated that the combination of CDK4/6 inhibitors and radiotherapy exhibited well-tolerated toxicity and promising efficacy. However, most clinical trials in combined therapy remain in the recruitment stage. Further work is required to seek optimal radiotherapy-drug combinations. In this review, we describe the effects and underlying mechanisms of CDK4/6 inhibitors as a radiosensitizer and discuss previous clinical studies to evaluate the prospects and challenges of this combination.

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Section: Clinical Studies Of Cdk4/6 Inhibitors In Combination With Ramentioning

confidence: 97%

Section: Clinical Studies Of Cdk4/6 Inhibitors In Combination With Ramentioning

confidence: 99%

CDK4/6 inhibitors: a novel strategy for tumor radiosensitization

Yang

Luo

Chen

et al. 2020

J Exp Clin Cancer Res

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“…In the retrospective analysis by Figura et al about brain metastases radiotherapy with curative intent, 5 out of the 15 patients received abemaciclib [42]. No information about CDK4/6i subgroups was given thus it is impossible to know if the patients experiencing radionecrosis after 4 fractions were on abemaciclib or palbociclib.…”

Section: Abemaciclibmentioning

confidence: 99%

CDK 4/6 inhibitors combined with radiotherapy: A review of literature

Bosacki

Bouleftour

Sotton

et al. 2021

Clinical and Translational Radiation Oncology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…In pivotal studies of CDK4/6 inhibitors, radiotherapy is allowed before systemic therapies beginning and it is preferable to avoid concomitance [ 68 , 69 , 70 ]. In literature, few data are reported that showed feasibility of radiotherapy in concomitance with CDK4/6 inhibitors, with a possible side effects arising (for example there are some reports of GI toxicity with RT on bone metastasis during abemaciclib) [ 71 , 72 , 73 , 74 ]. Another interesting issue about radiotherapy and CDK4/6 inhibitor is time of association because these drugs cause a cell blockage in G1 phase with consequently possible radioresistance.…”

Section: Radiotherapy Treatments Options and New Drugsmentioning

confidence: 99%

Diagnosis and Treatment of Bone Metastases in Breast Cancer: Radiotherapy, Local Approach and Systemic Therapy in a Guide for Clinicians

Marazzi

Orlandi

Manfrida

et al. 2020

Cancers

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The standard care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment for symptoms. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive settings are even more common—paving the way to a paradigm change of focal treatments role. In fact, according to immunophenotype, radiotherapy can be considered with radical intent in these settings of patients. The aim of this literature review is to analyze available clinical data on prognosis of bone metastases from breast cancer and benefits of available treatments for developing a practical guide for clinicians.

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CDK 4/6 inhibitors and stereotactic radiation in the management of hormone receptor positive breast cancer brain metastases

Cited by 54 publications

References 42 publications

CDK4/6 inhibitors: a novel strategy for tumor radiosensitization

CDK4/6 inhibitors: a novel strategy for tumor radiosensitization

CDK 4/6 inhibitors combined with radiotherapy: A review of literature

Diagnosis and Treatment of Bone Metastases in Breast Cancer: Radiotherapy, Local Approach and Systemic Therapy in a Guide for Clinicians

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