RESUMO
BACKGROUND: Evaluation of health-related quality of life (HR-QoL) among cancer patients has gained an increasing importance and is now a key determinant of anticancer treatments' value. HR-QoL has been assessed in trials testing cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in breast cancer (BC), using various questionnaires at different timepoints. HR-QoL reports from BC patients treated with CDK4/6i in the real-world setting are also available. METHODS: We systematically reviewed the literature, searching for full-length articles, and selected conference abstracts reporting data on HR-QoL in BC patients at any stage and of any molecular subtype treated with abemaciclib, palbociclib or ribociclib. RESULTS: A total of 533 full-length articles and 143 abstracts were retrieved. After screening for eligibility, 38 records were included (31 clinical trials; 7 real-world reports). Assessment methods were heterogeneous across studies in terms of questionnaires, evaluation timepoints and endpoints. Overall, adding CDK4/6i to endocrine therapy did not worsen patients' HR-QoL, with a positive trend towards pain improvement. Gastrointestinal scores (diarrhea, nausea and appetite loss) statistically favored the control arm among metastatic BC patients receiving abemaciclib, whereas they were superimposable in the early setting. The combination of palbociclib and endocrine therapy showed similar HR-QoL outcomes compared with endocrine therapy alone, but determined better scores compared with chemotherapy. HR-QoL was specifically assessed in premenopausal patients treated with ribociclib, showing similar scores compared with postmenopausal patients. CONCLUSIONS: Despite methodological heterogeneity does not allow a proper comparison, HR-QoL was generally maintained with CDK4/6i. However, differences between abemaciclib, palbociclib and ribociclib exist and mainly rely on the distinct safety profiles of the compounds. These differences should be acknowledged and taken into account in the clinical practice.
Assuntos
Neoplasias da Mama , Inibidores de Proteínas Quinases , Qualidade de Vida , Feminino , Humanos , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
BACKGROUND: High-dose oestrogen (HDE) is effective but toxic in postmenopausal women with advanced breast cancer (ABC). Prolonged oestrogen deprivation sensitises BC cell lines to estrogen and we hypothesised that third-generation aromatase inhibitors (AIs) would sensitise BCs to low-dose estradiol (LDE). METHODS: A single-arm phase II study of LDE (2 mg estradiol valerate daily) in postmenopausal women with estrogen receptor-positive (ER+) ABC. The primary end-point was clinical benefit (CB) rate. If LDE was ineffective, HDE was offered. If LDE was effective, retreatment with the pre-LDE AI was offered on progression. RESULTS: Twenty-one patients were recruited before the trial was closed early due to slow accrual; 19 were assessable for efficacy and toxicity. CB was seen in 5 in 19 patients (26%; 95% confidence interval 9.1-51.2%), all with prolonged SD (median duration 16.8 months; range 11.0-29.6). Treatment was discontinued for toxicity in 4 in 19 patients (21%) and 8 in 11 women without hysterectomy experienced vaginal bleeding (VB). After primary LDE failure, three patients received HDE and one achieved a partial response (PR). Following CB on LDE, four patients restarted pre-LDE AI and three achieved CB including one PR. Those with CB to LDE had a significantly longer duration of first-line endocrine therapy for ABC than those without (54.9 versus 16.8 months; p < 0.01) CONCLUSION: LDE is an effective endocrine option in women with evidence of prolonged sensitivity to AI therapy. LDE is reasonably well tolerated although VB is an issue. Re-challenge with the pre-LDE AI following progression confirms re-sensitisation as a true phenomenon.
Assuntos
Antineoplásicos Hormonais/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Estradiol/análogos & derivados , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Término Precoce de Ensaios Clínicos , Inglaterra , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/enzimologia , Neoplasias Hormônio-Dependentes/patologia , Seleção de Pacientes , Pós-Menopausa , Qualidade de Vida , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: To assess (18)F-2-fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography's ((18)F-FDG-PET/CT) potential clinical utility to allow early treatment changes during preoperative chemotherapy (PCT) in patients with early/locally advanced breast cancer (BC). PATIENTS AND METHODS: Sixty newly diagnosed early/locally advanced BC patients received 6-8 cycles of PCT. Optimal pathologic response (pR) was the absence of cancer cells in breast and axillary lymph nodes. All other conditions were defined as pathologic non-response (pNR). (18)F-FDG-PET/CT maximum standardised uptake value (SUV(max)) was measured at baseline and after 2 cycles of PCT. Metabolic response was defined as SUV(max) percentage changes (Δ-SUV) >50% and was compared with pR rates. RESULTS: Thirteen (22%) patients achieved pR; according to immunohistochemistry, 16% of ER-positive/HER2-negative patients, 29% and 27% of HER2-positive and triple negative patients respectively achieved pR. (18)F-FDG-PET/CT showed the highest specificity (38%) and negative predictive value (100%) in ER-positive/HER2-negative patients. In this subgroup, at a median follow-up of 36.6 months, median disease-free survival was still not reached in metabolic responders while it was 37 months in metabolic non-responders (p=0.049). DISCUSSION: Early metabolic non-response was always associated to pNR and poor prognosis in ER-positive/HER2-negative patients. In this subgroup, (18)F-FDG-PET/CT might be useful to select patients who will probably benefit from early therapeutic strategy modifications.