Treatment of advanced HR+/HER2- breast cancer with new targeted agents in combination with endocrine therapy: a review of efficacy and tolerability based on available randomized trials on everolimus, ribociclib, palbociclib and abemaciclib

Autor: Søren Cold, Anders Bonde Jensen, Tea M Bøttcher
Rok vydání: 2018
Předmět:
Oncology
Pyridines
Receptor
ErbB-2

Receptors
Cytoplasmic and Nuclear/genetics

Aminopyridines
Receptors
Cytoplasmic and Nuclear

Piperazines
030218 nuclear medicine & medical imaging
law.invention
DOUBLE-BLIND
chemistry.chemical_compound
0302 clinical medicine
Randomized controlled trial
law
Antineoplastic Combined Chemotherapy Protocols
Everolimus/administration & dosage
Pyridines/administration & dosage
Molecular Targeted Therapy
ADVANCED BREAST-CANCER
skin and connective tissue diseases
Abemaciclib
Benzimidazoles/administration & dosage
Randomized Controlled Trials as Topic
Drugs
Investigational/therapeutic use

food and beverages
Hematology
General Medicine
Receptor
ErbB-2/genetics

Treatment Outcome
POSTMENOPAUSAL WOMEN
Tolerability
030220 oncology & carcinogenesis
Antineoplastic Agents
Hormonal/administration & dosage

Disease Progression
Female
medicine.drug
GROWTH-FACTOR
medicine.medical_specialty
FIRST-LINE THERAPY
Antineoplastic Agents
Hormonal

Breast Neoplasms
Palbociclib
ANASTROZOLE
03 medical and health sciences
Breast cancer
Breast Neoplasms/drug therapy
Internal medicine
medicine
Aminopyridines/administration & dosage
Endocrine system
Humans
Radiology
Nuclear Medicine and imaging

Everolimus
TAMOXIFEN
Purines/administration & dosage
business.industry
Randomized Controlled Trials as Topic/statistics & numerical data
Cancer
Piperazines/administration & dosage
Drugs
Investigational

medicine.disease
PHASE-III
1ST-LINE TREATMENT
chemistry
Purines
Benzimidazoles
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
business
RESISTANCE
Molecular Targeted Therapy/methods
Zdroj: Bøttcher, T M, Cold, S & Jensen, A B 2019, ' Treatment of advanced HR+/HER2− breast cancer with new targeted agents in combination with endocrine therapy : a review of efficacy and tolerability based on available randomized trials on everolimus, ribociclib, palbociclib and abemaciclib ', Acta Oncologica, vol. 58, no. 2, pp. 147-153 . https://doi.org/10.1080/0284186X.2018.1532603
Bøttcher, T M, Cold, S & Jensen, A B 2019, ' Treatment of advanced HR+/HER2-breast cancer with new targeted agents in combination with endocrine therapy: a review of efficacy and tolerability based on available randomized trials on everolimus, ribociclib, palbociclib and abemaciclib ', Acta Oncologica, vol. 58, no. 2, pp. 147-153 . https://doi.org/10.1080/0284186X.2018.1532603
ISSN: 1651-226X
DOI: 10.1080/0284186X.2018.1532603
Popis: Introduction: Recently, new targeted agents have been developed, which can prolong the effect of endocrine treatment (ET) by targeting resistance pathways in HR+/HER2− advanced breast cancer. This review examines available studies of everolimus, an mTOR inhibitor, and the CDK 4/6 inhibitors ribociclib, palbociclib and abemaciclib in terms of efficacy, tolerability and safety. Material and methods: A systematic literature search was performed in Pubmed. Evaluation of the quality of the identified studies was based on selected elements from the GRADE guidelines. Results: The literature search yielded eight randomized trials that all presented a significant increase in the progression free survival (PFS)/time to progression (TTP) for the targeted agents plus ET vs ET only. The improvement was evident as first-line therapy with an increase in PFS of 10–11 months when adding a CDK4/6 inhibitor to ET, as well as in patients previously treated for metastatic disease, with an increase of 5–6 months. The common adverse events (AEs) of the CDK 4/6 inhibitors were due to myelosuppression. In addition, abemaciclib was associated with liver toxicity and diarrhea, and ribociclib with liver toxicity and QTcF prolongation. The most common grade 3/4 AE of everolimus was stomatitis. The majority (five) of the trials had no serious limitations, and thus the quality of evidence was high. Discussion: The new targeted agents are all associated with an improvement of the PFS with an acceptable tolerability, and they should be offered to women with advanced HR+/HER2− breast cancer both as first-line therapy as well as among patients previously treated in metastatic regimens. However, further data regarding the impact on overall survival are required to evaluate the full benefit for patients. Price and differences in AEs could become substantial arguments for the choice of therapy for the individual patient.
Databáze: OpenAIRE
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