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 |
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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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