Activity of CDK4/6 inhibitors and parameters affecting survival in elderly patients in age-subgroups: Turkish Oncology Group (TOG) retrospective study

BMC Cancer. 2024 Dec 30;24(1):1592. doi: 10.1186/s12885-024-13357-5.

Abstract

Highly selective inhibitors of cyclin-dependent kinase 4 and 6 (CDK4/6is) have emerged as a standart of care for first- and second-line therapies in combination with endocrine therapy (ET) for HR+/HER2- metastatic breast cancer (MBC) patients. It has been reported that combination therapy is more effective than ET alone and is safe in elderly patients as well as young patients. Nevertheless, elderly and very old patients with HR+/HER2-MBC treated with CDK4/6 inhibitor (CDK4/6i) combinations are relatively underrepresented in randomized controlled trials. To contribute to the literature, we investigated the real-world efficacy, factors associated with survival and the rates of adverse events (AEs) of the treatment with palbociclib or ribociclib plus ET in the HR+/HER2- MBC patient cohort over the age of 65 for age subgroups. In this retrospective study, 348 patients were divided into subgroups: 65-69 years old, 70-79 years old and 80 years and older. Median PFS (mPFS) for whole group was 18.3 (95% CI,14.3-22.3) months. There was no significant difference in mPFS between age groups (p = 0.75). The estimated median OS (mOS) was 39.5 (95% CI, 24.9-54.1) months and there was no significant difference between age groups (p = 0.15). There was a meaningfull numerical difference that did not reach statistical significance in patients who received CDK4/6i treatment as the first line for MBC. Grade 3-4 AEs were reported in 42.7% for the entire group, and neutropenia was the most common (37.3%). It can be concluded that combination therapy with palbociclib or ribociclib with an ET partner has similar efficacy and is safe among subgroups of older patients diagnosed with HR+/HER2-MBC.

Keywords: CDK 4/6 inhibitors; Geriatric population; Metastatic breast cancer.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aminopyridines / administration & dosage
  • Aminopyridines / adverse effects
  • Aminopyridines / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / mortality
  • Breast Neoplasms* / pathology
  • Cyclin-Dependent Kinase 4* / antagonists & inhibitors
  • Cyclin-Dependent Kinase 6* / antagonists & inhibitors
  • Female
  • Humans
  • Piperazines* / administration & dosage
  • Piperazines* / adverse effects
  • Piperazines* / therapeutic use
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Purines* / administration & dosage
  • Purines* / adverse effects
  • Purines* / therapeutic use
  • Pyridines* / administration & dosage
  • Pyridines* / adverse effects
  • Pyridines* / therapeutic use
  • Retrospective Studies
  • Turkey / epidemiology

Substances

  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • Piperazines
  • Purines
  • ribociclib
  • CDK4 protein, human
  • palbociclib
  • Protein Kinase Inhibitors
  • Pyridines
  • CDK6 protein, human
  • Aminopyridines