@article{3078145,
    title = "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",
    author = "Fountzilas, E. and Koliou, G.-A. and Vozikis, A. and Rapti, V. and Nikolakopoulos, A. and Boutis, A. and Christopoulou, A. and Kontogiorgos, I. and Karageorgopoulou, S. and Lalla, E. and Tryfonopoulos, D. and Boukovinas, I. and Rapti, C. and Nikolaidi, A. and Karteri, S. and Moirogiorgou, E. and Binas, I. and Mauri, D. and Aravantinos, G. and Zagouri, F. and Saridaki, Z. and Psyrri, A. and Bafaloukos, D. and Koumarianou, A. and Res, E. and Linardou, H. and Mountzios, G. and Razis, E. and Fountzilas, G. and Koumakis, G.",
    journal = "ESMO open",
    year = "2020",
    volume = "5",
    number = "4",
    publisher = "BMJ Publishing Group",
    doi = "10.1136/esmoopen-2020-000774",
    keywords = "cyclin dependent kinase 4;  cyclin dependent kinase 6;  cyclin dependent kinase inhibitor;  fulvestrant;  letrozole;  palbociclib;  ribociclib;  tamoxifen;  taxane derivative;  antineoplastic agent;  CDK4 protein, human;  CDK6 protein, human;  cyclin dependent kinase 4;  cyclin dependent kinase 6, adult;  aged;  anemia;  Article;  blood toxicity;  breast cancer;  cancer chemotherapy;  cancer hormone therapy;  cancer patient;  cancer survival;  clinical outcome;  cohort analysis;  cost benefit analysis;  data analysis;  diarrhea;  drug cost;  drug dose reduction;  drug tolerability;  drug withdrawal;  economic aspect;  estrogen receptor positive breast cancer;  fatigue;  female;  fever;  health care cost;  human;  human epidermal growth factor receptor 2 negative breast cancer;  incidence;  major clinical study;  medical care;  multiple cycle treatment;  nausea;  neutropenia;  overall survival;  postmenopause;  progesterone receptor positive breast cancer;  progression free survival;  reimbursement;  retrospective study;  skin disease;  stomatitis;  survival analysis;  thrombocytopenia;  vomiting;  breast tumor;  endocrine system;  middle aged;  prospective study, Aged;  Antineoplastic Combined Chemotherapy Protocols;  Breast Neoplasms;  Cyclin-Dependent Kinase 4;  Cyclin-Dependent Kinase 6;  Endocrine System;  Female;  Humans;  Middle Aged;  Prospective Studies;  Retrospective Studies",
    abstract = "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. © Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ on behalf of the European Society for Medical Oncology."
}