The impact of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) on the incidence of alopecia in patients with metastatic breast cancer (BC)

Background: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8–86.8) vs. 40.2 Gy (12.5–83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 μmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.

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

Current Medical Research and Opinion ◽

10.1080/03007995.2017.1348344 ◽

2017 ◽

Vol 33 (9) ◽

pp. 1559-1569 ◽

Cited By ~ 19

Author(s):

Burak Bilgin ◽

Mehmet A.N. Sendur ◽

Didem Şener Dede ◽

Muhammed Bülent Akıncı ◽

Bülent Yalçın

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Kinase Inhibitors ◽

Metastatic Breast ◽

Cyclin Dependent Kinase ◽

Comprehensive Review ◽

A Current

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The impact of quality of life (QL) scores on survival in patients with metastatic breast cancer (MBC)

European Journal of Cancer ◽

10.1016/s0959-8049(98)80147-0 ◽

1998 ◽

Vol 34 ◽

pp. S39

Author(s):

Alan Coates

Keyword(s):

Breast Cancer ◽

Quality Of Life ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

The Impact

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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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