4CPS-293 Efficacy and safety of cyclin dependent kinase inhibitors in 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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Abstract OT-31-01: A phase II study to evaluate the efficacy and safety of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer: PEMBRACA trial

10.1158/1538-7445.sabcs20-ot-31-01 ◽

2021 ◽

Author(s):

Laura Cortesi ◽

Marta Venturelli ◽

Federica Caggia ◽

Luigi Marcheselli ◽

Annita Gozzi ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Metastatic Breast ◽

Efficacy And Safety

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Efficacy and safety of low-dose metronomic chemotherapy with capecitabine in heavily pretreated patients with metastatic breast cancer

European Journal of Cancer ◽

10.1016/j.ejca.2011.06.040 ◽

2012 ◽

Vol 48 (1) ◽

pp. 24-29 ◽

Cited By ~ 54

Author(s):

P. Fedele ◽

A. Marino ◽

L. Orlando ◽

P. Schiavone ◽

A. Nacci ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Low Dose ◽

Metastatic Breast ◽

Metronomic Chemotherapy ◽

Efficacy And Safety ◽

Heavily Pretreated ◽

Pretreated Patients

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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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