Date of Award
Selective Evidence-Based Medicine Review
Master of Science in Health Sciences - Physician Assistant
Physician Assistant Studies
John Cavenagh, MBA, PhD, PA-C
Objective: The objective of this selective EBM review is to determine whether or not CDK 4/6 inhibitors, in combination with anti-estrogen therapy, improve morbidity and mortality for women with advanced breast cancer compared to anti-estrogen monotherapy.
Study Design: Systematic review of three randomized-controlled trials. All three articles were published in English between 2015 and 2016.
Data Sources: Two randomized, double-blinded, placebo-controlled trials and one open-label randomized controlled trial found using PubMed and NCBI.
Outcomes Measured: Each study assessed morbidity and mortality based on progression-free survival or overall clinical benefit (stable disease, partial response, or complete response by 24 weeks).
Results: All three studies showed significant prolongation of progression-free survival in patients that received treatment with anti-estrogen therapy plus an oral CDK 4/6 inhibitor for their estrogen receptor-positive, HER2neu negative metastatic breast cancer compared to anti-estrogen therapy alone or with placebo. Cristofanilli et al. found that median progression-free survival improved from 4.6 months to 9.5 months with combination therapy. Similar results were seen in Finn et al. with median progression-free survival of 20.2 months in those receiving combination therapy, compared to 10.2 months in women treated with anti-estrogen therapy alone. In the study by Hortobagyi et al., the progression-free survival rate at 18 months for those treated with CDK4/6 inhibitor was 63%, compared to 42.2% in the placebo group.
Conclusions: These studies suggest that cyclin dependent kinase 4/6 inhibitors used in conjunction with anti-estrogen therapy should be considered as an efficacious treatment regimen for postmenopausal patients with hormone receptor-positive, HER2neu negative advanced breast cancer. Finn and Hortobagyi, and colleagues, investigated the use of an aromatase inhibitor, letrozole, for anti-estrogen therapy. Cristofanilli and colleagues studied the efficacy of an estrogen receptor downregulator, fulvestrant. Additionally, palbociclib was used for inhibition of the CDK4/6 pathway in two studies, while ribociclib was used in the other. Improvement in progression-free survival and overall response was seen in all three studies regardless of the combination of drugs being used.
Mercado, Kayla, "Do CDK 4/6 Inhibitors, in Combination with Anti-Estrogen Therapy, Improve Morbidity and Mortality in Women with Advanced Breast Cancer Compared to Anti-Estrogen Therapy Alone?" (2018). PCOM Physician Assistant Studies Student Scholarship. 329.