The implementation of CDK 4/6 inhibitors and its impact on treatment choices in HR+/HER2- advanced breast cancer patients: A study of the Dutch SONABRE Registry

Abstract

In August 2017, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy have been reimbursed in the Netherlands for patients with hormone receptor positive (HR+), HER2 negative (HER2-) advanced breast cancer (ABC). This study evaluates the implementation of CDK4/6 inhibitors and changes in treatment choices in the Netherlands. All patients diagnosed with HR+/HER2- ABC in 2009 to 2018 in seven hospitals were selected from the Southeast Netherlands Advanced Breast cancer (SONABRE) registry. The 2-year cumulative use of CDK4/6 inhibitors since reimbursement date (August 2017) was assessed using competing-risk methodology in two cohorts. The first cohort included patients with ABC diagnosis between August 2017 and December 2018. The second cohort included patients with ABC diagnosis between 2009 and August 2017, and still alive on August 1, 2017. In addition, treatment choices in the first three lines of therapy in calendar years 2009 to 2018 were evaluated for the total study population. Among patients diagnosed since August 2017 (n = 214), 50% (95% confidence interval [CI] = 43-57) received CDK4/6 inhibitors within 2 years beyond diagnosis. Of eligible patients diagnosed before August 2017 (n = 417), 31% (95% CI = 27-36) received CDK4/6 inhibitors within 2 years following reimbursement. Another 20% of both cohorts are still CDK4/6 inhibitor naïve and on first-line therapy. The use of chemotherapy decreased in first two lines of therapy between 2009 and 2018 (first-line: 29%-13%; second-line: 26%-19%). The implementation rate of CDK4/6 inhibitors since reimbursement is currently 50% within 2 years beyond diagnosis and is expected to increase further. The implementation of targeted therapy decreased the use of chemotherapy as first-line therapy.

Keywords: CDK4/6 inhibitors; breast cancer; implementation; metastatic disease; real-world.

FIGURE 1

Patient selection for the evaluation of treatment choices and the implementation of CDK4/6 inhibitors. CDK4/6, cyclin‐dependent kinase 4/6

FIGURE 2

The use of CDK4/6 inhibitors in patients diagnosed with HR+/HER2− ABC since August 2017. (A) Cumulative use of CDK4/6 inhibitors since date of ABC diagnosis by competing risk methodology. (B) First‐line treatment choice for all patients (n = 214), and second‐line treatment choice for CDK4/6 inhibitor naïve patients (n = 71). ABC, advanced breast cancer; CDK4/6, cyclin‐dependent kinase 4/6; CDK4/6i, CDK4/6 inhibitors; ET, endocrine therapy; HER2, human epidermal growth factor receptor 2; HR, hormone receptor [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

The use of CDK4/6 inhibitors since the reimbursement date in patients diagnosed with HR+/HER2− ABC between 2009 and August 2017, and alive on August 1, 2017. (A) Cumulative use of CDK4/6 inhibitors since reimbursement date by competing risk methodology. (B) First‐given new line of therapy since reimbursement date in patients that switched systemic therapy (n = 248). ABC, advanced breast cancer; CDK4/6, cyclin‐dependent kinase 4/6; CDK4/6i, CDK4/6 inhibitors; ET, endocrine therapy; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; mTOR, mTOR inhibitors [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 4

Treatment choices in all patients diagnosed with HR+/HER2− ABC from 2009 until 2018 per calendar year in first, second and third line of therapy. Treatment choices are shown from 2010 in second‐line and from 2011 in third‐line to present a representative distribution of patients in next‐line treatment. ABC, advanced breast cancer; HER2, human epidermal growth factor receptor 2; HR, hormone receptor [Color figure can be viewed at wileyonlinelibrary.com]