A current and comprehensive review of cyclin-dependent kinase inhibitors for the treatment of metastatic breast cancer

Targeting cell cycle has become the gold standard for metastatic breast cancer (MBC), being cyclin-dependent kinase inhibitors (CDKIs) cornerstones of its treatment, alongside radiotherapy (RT). To date, no definite evidence regarding safety and efficacy of the combination of CDKIs plus radiotherapy (RT) is currently available. Purpose of this review is to collect data in favor or against the feasibility of the association of CDKIs + RT, describing its potential adverse events. Our review shows how CDKI + RT allows an overall satisfying disease control, proving to be effective and causing a grade of toxicity mainly influenced by the site of irradiation, leaning to favourable outcomes for sites as liver, spine or brain and to poorer outcomes for thoracic lesions or sites close to viscera; controversial evidence is instead for bone treatment. Toxicity also varies from patient to patient. To sum up, our contribution enriches and enlightens a still indefinite field regarding the feasibility of CDKIs + RT, giving cues for innovative clinical management of hormone-responsive MBC.

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Hormone therapy for premenopausal women with metastatic breast cancer: combinations with cyclin-dependent kinase inhibitors

Tumors of female reproductive system ◽

10.17650/1994-4098-2019-15-2-30-41 ◽

2019 ◽

Vol 15 (2) ◽

pp. 30-41

Author(s):

E. V. Artamonova ◽

E. I. Kovalenko

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Hormone Therapy ◽

Randomized Trials ◽

Kinase Inhibitors ◽

Treatment Strategies ◽

Metastatic Breast ◽

Premenopausal Women ◽

Cyclin Dependent Kinase ◽

Ovarian Suppression

This article discusses the problems associated with the search of the most effective treatment strategies for HER2-negative metastatic breast cancer in premenopausal women. Until recently, ovarian suppression and hormone therapy had been the main treatments used in this group of patients. The development of palbociclib, called a “breakthrough therapy”, as well as promising results of trials evaluating the efficacy of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors added to hormone therapy in postmenopausal women suggested a need for the assessment of this treatment regimen in combination with ovarian suppression in younger patients.According to the results of randomized trials and subgroup analysis, the addition of a CDK4/6 inhibitor to ovarian suppression and hormonal therapy significantly increases survival. The safety profile is similar to that of older patients. Randomized trials comparing the efficacy of palbociclib + ovarian suppression + aromatase inhibitor vs. chemotherapy in premenopausal women demonstrated significant benefits of a new treatment strategy: a CDK4/6 inhibitor as a part of combination therapy reduced the risk of progression by 36 % compared to capecitabine.

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4CPS-293 Efficacy and safety of cyclin dependent kinase inhibitors in metastatic breast cancer

10.1136/ejhpharm-2021-eahpconf.125 ◽

2021 ◽

Author(s):

L Cantarelli ◽

JA Morales Barrios ◽

S Garcia Gil ◽

B Del Rosario Garcia ◽

GJ Nazco Casariego ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Kinase Inhibitors ◽

Metastatic Breast ◽

Cyclin Dependent Kinase ◽

Efficacy And Safety

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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

Therapeutic Advances in Drug Safety ◽

10.1177/2042098617722516 ◽

2017 ◽

Vol 8 (11) ◽

pp. 337-347 ◽

Cited By ~ 11

Author(s):

Kyrillus S. Shohdy ◽

Shaimaa Lasheen ◽

Loay Kassem ◽

Omar Abdel-Rahman

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Safety Profile ◽

Meta Analysis ◽

Metastatic Breast ◽

High Grade ◽

Cyclin Dependent Kinase ◽

Breast Cancer Patients ◽

Randomized Phase Ii

Background: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors show promising results in metastatic breast cancer. However, an increased incidence of adverse events is remarkable. Among others, gastrointestinal (GI) involvement is of momentous impact on patients and their quality of life. Methods: Our search included PubMed, ASCO, ESMO and SABCS databases. Randomized phase II/III trials in metastatic breast cancer receiving CDK4/6 inhibitors were identified and considered relevant based on providing a sufficient safety profile on the incidence of adverse GI effects. Results: Of the 999 records initially screened for relevance, 33 articles were found relevant and 4 studies were finally eligible for meta-analysis with a total of 2007 patients. The relative risk (RR) for all-grade nausea was 1.48 [95% confidence interval (CI): 1.12–1.93, p = 0.005], vomiting was 1.74 (95% CI: 1.09–2.76, p = 0.02), decreased appetite was 1.42 (95% CI: 1.07–1.88, p = 0.02), and for diarrhea it was 1.44 (95% CI: 1.19–1.74, p = 0.0002). Meanwhile, the RR for high-grade nausea was 1.10 (95% CI: 0.29–4.13, p = 0.89), vomiting was 1.38 (95% CI: 0.25–7.75, p = 0.72), decreased appetite was 4.00 (95% CI: 0.87–18.37, p = 0.07), and high-grade diarrhea was 1.19 (95% CI: 0.44–3.21, p = 0.73). Conclusion: Selective CDK4/6 inhibitors were not associated with higher-grade GI toxicities reflecting a well-tolerated safety profile. Regarding the increase in all-grade GI toxicities, it needs further caution with addition of cytotoxic chemotherapy.

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Observational study of clinical outcomes of eribulin mesylate in metastatic breast cancer after cyclin-dependent kinase 4/6 inhibitor therapy

Future Oncology ◽

10.2217/fon-2019-0537 ◽

2019 ◽

Vol 15 (34) ◽

pp. 3935-3944 ◽

Cited By ~ 4

Author(s):

Sarah S Mougalian ◽

Bruce A Feinberg ◽

Edward Wang ◽

Karenza Alexis ◽

Debanjana Chatterjee ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Clinical Outcomes ◽

Kinase Inhibitor ◽

Objective Response ◽

Metastatic Breast ◽

Progression Free Survival ◽

Cyclin Dependent Kinase ◽

Eribulin Mesylate ◽

Free Survival

Aim: To examine the effectiveness of eribulin mesylate for metastatic breast cancer post cyclin-dependent kinase inhibitor (CDKi) 4/6 therapy. Materials & methods: US community oncologists reviewed charts of patients who had received eriublin from 3 February 2015 to 31 December 2017 after prior CDKi 4/6 therapy and detailed their clinical/treatment history, clinical outcomes (lesion measurements, progression, death) and toxicity. Results: Four patient cohorts were created according to eribulin line of therapy: second line, third line, per US label and fourth line with objective response rates/clinical benefit rates of 42.2%/58.7%, 26.1%/42.3%, 26.7%/54.1% and 17.9%/46.4%, respectively. Median progression-free survival/6-month progression-free survival (79.5% of all patients censored) by cohort was: 9.7 months/77.3%, 10.3 months/71.3%, not reached/70.4% and 4.0 months/0.0%, respectively. Overall occurrence of neutropenia = 23.5%, febrile neutropenia = 1.3%, peripheral neuropathy = 10.1% and diarrhea = 11.1%. Conclusion: Clinical outcome and adverse event rates were similar to those in clinical trials and other observational studies. Longer follow-up is required to confirm these findings.

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