Real-world clinical outcome and toxicity data and economic aspects in patients with advanced breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy: the experience of the Hellenic Cooperative Oncology Group

ESMO Open. 2020 Aug;5(4):e000774. doi: 10.1136/esmoopen-2020-000774.


Background: We evaluated real-world clinical outcomes and toxicity data and assessed treatment-related costs in patients with advanced breast cancer who received treatment with cyclin-dependent kinase inhibitors (CDKi).

Patients and methods: We conducted a prospective-retrospective analysis of patients with advanced hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who received a CDKi, in combination with endocrine therapy, at any line of treatment. The primary endpoint was progression-free survival (PFS). Cost analysis was conducted from a public third-payer (National Organization for Healthcare Services Provision (EOPYY)) perspective, assessing only costs related to direct medical care, including drug therapy costs and adverse drug reaction (ADR)-related costs.

Results: From July 2015 to October 2019, 365 women received endocrine therapy combined with CDKi; median age was 61 years, postmenopausal 290 (80.6%) patients. CDKi were administered as first-line treatment in 149 (40.9%) patients, second-line treatment in 96 (26.4%) and third-line treatment and beyond in 119 (32.7%) patients. The most common adverse events were neutropenia, anaemia, thrombocytopenia and fatigue. Grade 3-4 adverse events occurred in 86 (23.6%) patients, whereas 8 (2.2%) patients permanently discontinued treatment due to toxicity. The median PFS for patients who received CDKi as first-line, second-line and third-line treatment and beyond was 18.7, 12 and 7.4 months, respectively. The median overall survival since the initiation of CDKi treatment was 29.9 months (95% CI: 23.0-not yet reached (NR)). The mean pharmaceutical therapy cost estimated per cycle was 2 724.12 € for each patient, whereas the main driver of the ADR-related costs was haematological adverse events.

Conclusions: Treatment with CDKi was well tolerated, with a low drug discontinuation rate. Patients who received CDKi as first-line treatment had improved PFS and OS compared with second-line treatment and beyond. The main component of direct medical costs assessed in the cost analysis comprises CDKi pharmaceutical therapy costs.

Trial registration number: NCT04133207.

Keywords: aromatase inhibitors; endocrine treatment; health economics; hormone receptor-positive; real-world evidence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols
  • Breast Neoplasms* / drug therapy
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • Endocrine System
  • Female
  • Humans
  • Middle Aged
  • Prospective Studies
  • Retrospective Studies


  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6

Associated data