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1.
Gan To Kagaku Ryoho ; 51(9): 935-938, 2024 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-39462630

RESUMO

A 74-year-old woman was diagnosed with invasive breast ductal carcinoma, cT2N0M1 (PUL), stage Ⅳ, and treated with abemaciclib and letrozole. The day after drug administration, the patient developed a fever of 38℃ and dyspnea upon exertion, and was diagnosed with drug-induced pneumonia. Steroid pulse therapy was administered during hospitalization, and the patient was discharged after the dose of prednisolone was gradually reduced. This case shows that, when abemaciclib is administered, drug-induced lung injury can occur within 1 week.


Assuntos
Aminopiridinas , Benzimidazóis , Neoplasias da Mama , Lesão Pulmonar , Humanos , Feminino , Idoso , Neoplasias da Mama/tratamento farmacológico , Aminopiridinas/administração & dosagem , Aminopiridinas/efeitos adversos , Aminopiridinas/uso terapêutico , Benzimidazóis/efeitos adversos , Benzimidazóis/administração & dosagem , Benzimidazóis/uso terapêutico , Lesão Pulmonar/induzido quimicamente , Letrozol/administração & dosagem , Letrozol/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Ductal de Mama/tratamento farmacológico
2.
Front Immunol ; 15: 1430648, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39229263

RESUMO

Background: Angioimmunoblastic T-cell lymphoma (AITL) is known for its unfavorable survival prognosis. Chidamide has shown efficacy in relapsed/refractory AITL, but its efficacy in newly diagnosed AITL is uncertain. Objective: This retrospective research aimed to evaluate the effectiveness and safety of chidamide when used with doxorubicin, cyclophosphamide, prednisone, and vincristine (CHOP) in comparison to CHOP by itself for individuals newly diagnosed with AITL, and to examine the impact of transplantation. Method: This was an analysis that compared outcomes among patients who received chidamide + CHOP on a clinical trial vs. historical controls who received CHOP alone, enrolling a total of sixty-six treatment-naive AITL patients between April 2014 and November 2022. Among them, thirty-three received chidamide in addition to CHOP (chidamide group), while thirty-three received CHOP alone (control group). The clinical characteristics were balanced between the two groups. All patients were scheduled to undergo up to six courses of treatment before transplantation. Results: The chidamide group had a significantly longer median overall survival (OS) compared to the control group, with a median OS that was not reached, as opposed to 20 months in the control group (p = 0.002). In the control group, the median progression-free survival (PFS) was 11 months, while in the chidamide group, it was 22 months (p = 0.080). In the high-risk group (IPI ≥ 3), the chidamide group demonstrated notably superior complete response (CR) and overall response rate (ORR) compared to the control cohort (p = 0.002, p = 0.034). The PFS and OS in the chidamide group were not reached, and there were significant differences compared to the control group (p = 0.007, p = 0.003). The median OS of the transplanted group was longer than the non-transplanted group (p = 0.004). On multivariate analysis, chidamide group reduced the hazards of death in the total cohort. Conclusion: As the study was non-random and retrospective, Chidamide combined with chemotherapy should be tested in randomized trials given its potential to improve prognosis in treatment-naive AITL patients. Furthermore, autologous hematopoietic stem cell transplantation (auto-HSCT) has demonstrated enhanced overall survival in individuals with AITL. Clinical trial registration: https://clinicaltrials.gov/, NCT03268889.


Assuntos
Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aminopiridinas/uso terapêutico , Aminopiridinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzamidas/uso terapêutico , Benzamidas/administração & dosagem , Benzamidas/efeitos adversos , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Linfoma de Células T/mortalidade , Linfoma de Células T/terapia , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/diagnóstico , Prednisona/uso terapêutico , Prednisona/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento , Vincristina/uso terapêutico , Vincristina/administração & dosagem
3.
JNCI Cancer Spectr ; 8(5)2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39254653

RESUMO

BACKGROUND: Cyclin-dependent kinases (CDK) 4/6 inhibitors have significantly improved outcomes for patients with ER+/HER2- breast cancer. Nevertheless, they differ from each other in terms of chemical, biological, and pharmacological features, as well as toxicity profiles. We aim to determine whether QTc prolongation is caused by CDK4/6i in general or if it is associated with ribociclib only. METHODS: We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing the prevalence of QTc prolongation as an adverse event in HR+ breast cancer patients treated with CDK4/6i vs those without CDK4/6i. We pooled relative risk (RR) and mean difference (MD) with 95% confidence interval (CI) for the binary endpoint of QT prolongation. RESULTS: We included 14 RCTs comprising 16 196 patients, of whom 8576 underwent therapy with CDK4/6i. An increased risk of QTc prolongation was associated with the use of CDK4/6i (RR = 2.35, 95% CI = 1.67 to 3.29, P < .001; I2 = 44%). Subgroup analyses revealed a significant increase in the QTc interval for the ribociclib and palbociclib cohorts. The ribociclib subgroup showed a relative risk of 3.12 (95% CI = 2.09 to 4.65, P < .001; I2 = 12%), whereas the palbociclib subgroup had a relative risk of 1.51 (95% CI = 1.05 to 2.15, P = .025; I2 = 0%). CONCLUSION: Palbociclib was associated with QTc prolongation; however, the relative risk for any grade QTc was quantitively twice with ribociclib. Furthermore, grade 3 QTc prolongations were observed exclusively with ribociclib. These results are important for guiding clinical decision-making and provide reassurance regarding the overall safety profile of this drug class.


Assuntos
Aminopiridinas , Neoplasias da Mama , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Síndrome do QT Longo , Piperazinas , Inibidores de Proteínas Quinases , Purinas , Piridinas , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Purinas/efeitos adversos , Purinas/uso terapêutico , Purinas/administração & dosagem , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Síndrome do QT Longo/induzido quimicamente , Aminopiridinas/efeitos adversos , Aminopiridinas/uso terapêutico , Aminopiridinas/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Piperazinas/efeitos adversos , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/administração & dosagem , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Piridinas/administração & dosagem , Feminino , Roscovitina/efeitos adversos , Benzimidazóis
4.
Lung Cancer ; 196: 107954, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39303401

RESUMO

OBJECTIVES: Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) inhibitor, causes distinct adverse events (AEs), including hyperlipidemia and central nervous system (CNS) disorders. Although dose modifications are recommended to manage these AEs, whether dose modifications can achieve optimal blood lorlatinib concentrations and reduce the incidence of lorlatinib-induced AEs remains unclear. Therefore, we investigated the association between lorlatinib exposure and AEs in each patient. MATERIALS AND METHODS: We retrospectively reviewed patients with advanced ALK-rearranged non-small cell lung cancer treated with lorlatinib between November 2018 and July 2022. Serum lorlatinib concentrations were assessed using high-performance liquid chromatography-tandem mass spectrometry. All AEs were evaluated using the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: The median age of the 55 eligible patients was 59 years (range: 23-79 years). All patients were administered lorlatinib after first line ALK-tyrosine kinase inhibitor failure. Grade ≥ 3 AEs occurred in 25 patients (25/55, 45 %), including hyperlipidemia in 17 (17/55, 31 %), CNS disorders in 7 (7/55, 13 %), and edema in 6 (6/55, 11 %). Dose modification was required in 23 patients (23/55, 42 %). Among the 36 patients with available data on serum lorlatinib levels at day 28 (±14) and no drug dose modifications, lorlatinib serum concentrations were significantly higher in patients with grade ≥ 3 AEs than in those without AEs (median: 462 ng/mL vs. 177 ng/mL, p < 0.01). In eight patients with data on serial lorlatinib serum concentrations following dose modifications, lorlatinib serum concentrations were effectively reduced, facilitating the ongoing administration of lorlatinib. Additionally, no significant difference was observed in the landmark analysis of progression-free survival between patients with dose modification within the first 16 weeks and those without (median: 24.8 months vs. 10.1 months, p = 0.46). CONCLUSION: Dose modification of lorlatinib was associated with successful management of AEs and decreased serum concentration of lorlatinib.


Assuntos
Aminopiridinas , Carcinoma Pulmonar de Células não Pequenas , Lactamas , Neoplasias Pulmonares , Pirazóis , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Adulto , Estudos Retrospectivos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Aminopiridinas/efeitos adversos , Aminopiridinas/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Lactamas/efeitos adversos , Adulto Jovem , Pirazóis/efeitos adversos , Pirazóis/administração & dosagem , Pirazóis/farmacocinética , Pirazóis/uso terapêutico , Lactamas Macrocíclicas/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Quinase do Linfoma Anaplásico/genética
5.
Asian Pac J Cancer Prev ; 25(9): 3039-3049, 2024 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-39342581

RESUMO

AIM: Assessment of CBR, PFS, QOL and toxicity profile of palbociclib and ribociclib. METHODS: This is an interventional concurrent randomised phase III open label clinical trial. It took place at the Oncology Centre Mansoura University, Egypt from July 2022 till December 2023. Patients with pathologically proved ER+ HER2- metastatic breast cancer who either progressed on adjuvant hormonal or progressed on 1st line hormonal for metastatic disease. Patients in arm A received palbociclib 125 mg/day orally for 3 weeks and 1 week rest, plus fulvestrant. Patients in Arm B received ribociclib at a dose of 600 mg, administered orally once daily for 3 weeks and 1 week rest, plus fulvestrant. Pre- and peri-menopausal women received the LHRH agonist goserelin. Patients who lost their endorsement and were considered to be lost to follow up. Quality of life was analysed using the (EORTC) quality-of-life questionnaire (QLQ)-C30 V3.0. Patients were asked to complete the questionnaires at screening; at the 2nd and 6th month. Toxicity was assessed and graded using (CTCAE) v5.0. Patients were evaluated clinically for response and toxicity monthly and radiologically by CT and tumor markers/ 3 months. Treatment continued until objective Progressive Disease (PD), symptomatic deterioration, unacceptable toxicity or death. RESULTS: Both arms had similar baseline characteristics. There was no statistically significant difference regarding the CBR (58.6% for both arms at 6 months and 13.8% in the palbociclib VS 17.2% in the ribociclib arm at 12 months). The median PFS to the whole population was 13 months. COX multivariate analysis revealed that postmenopausal had 2.85 more likely to survive than premenopausal patients. Patients with ECOG performance status 2 and 3 are 0.13 and 0.39 less likely to survive compared to patients with PS 1. Dose reduction increased the likelihood of survival 3.36 compared with no dose reduction. The median PFS was 13.67 months in the palbociclib arm and 12.69 months in the ribociclib arm with no statistically significant difference. During follow up, there was statistically significant improvement in insomnia in both arms and constipation in the palbociclib arm alone. Comparing the two arms, no statistically significant deterioration in the QOL domains except in fatigue and financial difficulties, with more deterioration in the palbociclib arm. Regarding common toxicities there was no statistically significant difference between the 2 arms. CONCLUSIONS: Both Ribociclib and palbociclib have similar CBR, PFS and toxicity profile.


Assuntos
Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Fulvestranto , Piperazinas , Purinas , Piridinas , Qualidade de Vida , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Aminopiridinas/administração & dosagem , Piridinas/administração & dosagem , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Purinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Fulvestranto/administração & dosagem , Adulto , Seguimentos , Prognóstico , Taxa de Sobrevida
6.
Cancer Med ; 13(15): e7408, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39136200

RESUMO

BACKGROUND: The MONALEESA­7 and ­2 phase 3 randomized trials demonstrated a statistically significant progression­free survival (PFS) and overall survival (OS) benefit with initial ribociclib + endocrine therapy (ET) versus placebo + ET in pre­ and postmenopausal patients with hormone receptor­positive (HR+)/human epidermal growth factor receptor 2­negative (HER2−) advanced breast cancer (ABC), respectively. Similar trends were observed in Asian subgroup analyses. This phase 2 bridging study of initial ET + ribociclib enrolled pre­ and postmenopausal patients with HR+/HER2­ ABC from China and was conducted to demonstrate consistency of PFS results in a Chinese population relative to the global MONALEESA­7 and ­2 studies. METHODS: Patients were randomized (1:1) to ET (nonsteroidal aromatase inhibitor + goserelin for premenopausal patients; letrozole for postmenopausal patients) + either ribociclib or placebo. The primary endpoint was investigator­assessed PFS. RESULTS: As of April 25, 2022, the median follow­up was 34.7 months in both cohorts. In the premenopausal cohort, median PFS was 27.6 months in the ribociclib arm (n = 79) versus 14.7 months in the placebo arm (n = 77) (hazard ratio 0.67 [95% CI: 0.45, 1.01]). In the postmenopausal cohort, median PFS was not reached in the ribociclib arm versus 18.5 months in the placebo arm (n = 77 in each arm) (hazard ratio 0.40 [95% CI: 0.26, 0.62]). Data also suggested improvements in secondary efficacy endpoints, although OS data were not mature. The safety profile in this population was consistent with that in global studies. CONCLUSIONS: These data demonstrate a favorable benefit­risk profile for ribociclib + ET in Chinese patients.


Assuntos
Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Letrozol , Pós-Menopausa , Purinas , Receptor ErbB-2 , Receptores de Estrogênio , Humanos , Aminopiridinas/administração & dosagem , Aminopiridinas/uso terapêutico , Aminopiridinas/efeitos adversos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Purinas/administração & dosagem , Purinas/efeitos adversos , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Receptores de Estrogênio/metabolismo , Letrozol/administração & dosagem , Letrozol/uso terapêutico , Adulto , China , Idoso , Receptores de Progesterona/metabolismo , Pré-Menopausa , Intervalo Livre de Progressão , Gosserrelina/administração & dosagem , Gosserrelina/uso terapêutico , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/uso terapêutico , População do Leste Asiático
7.
BMC Cancer ; 24(1): 1018, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39152401

RESUMO

BACKGROUND: The current standard first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2 negative (HR + /HER2 -) advanced breast cancer (ABC) is a combination of aromatase inhibitor (AI) plus CDK4/6 inhibitors (CDK4/6i). Direct comparison trials of different CDK4/6i are scarce. This real-world study compared the effectiveness of first-line AI plus ribociclib versus palbociclib. METHODS: This multicenter retrospective cohort study, conducted in six cancer centers in Thailand, enrolled patients with HR + /HER2 - ABC treated with first-line AI, and either ribociclib or palbociclib. Propensity score matching (PSM) was performed. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), time to chemotherapy (TTC), and adverse events. RESULTS: Of the 250 patients enrolled, 134 patients with ribociclib and 49 patients with palbociclib were captured after PSM. Baseline characteristics were well-balanced between groups. Median PFS in patients receiving ribociclib and palbociclib were 27.9 and 31.8 months, respectively (hazard ratio: 0.87; 0.55-1.37). The median OS in the AI + ribociclib arm was 48.7 months compared to 59.1 months in the AI + palbociclib arm (hazard ratio: 0.55; 0.29-1.05). The median TTC in the AI + palbociclib group was 56 months, but not reached in the AI + ribociclib group (p = 0.42). The ORR of AI + ribociclib and AI + palbociclib were comparable (40.5% vs. 53.6%, p = 0.29). Patients receiving palbociclib demonstrated a higher proportion of neutropenia compared to those receiving ribociclib, despite a similar dose reduction rate (p = 0.28). Hepatitis rate was similar between the ribociclib (21%) and palbociclib groups (22%). Additionally, a low incidence of QT prolongation was observed in both the ribociclib (5%) and palbociclib groups (4%). CONCLUSION: This preliminary analysis of a real-world study demonstrated the comparable effectiveness of ribociclib and palbociclib with AI as an initial therapy for HR + /HER2 - ABC. No statistically significant difference in PFS, OS, and TTC was found in patients treated with AI combined with palbociclib or ribociclib. Longer follow-up and further prospective randomized head-to-head studies are warranted.


Assuntos
Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Piperazinas , Purinas , Piridinas , Receptor ErbB-2 , Receptores de Estrogênio , Humanos , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Piperazinas/uso terapêutico , Feminino , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Aminopiridinas/administração & dosagem , Aminopiridinas/uso terapêutico , Aminopiridinas/efeitos adversos , Purinas/administração & dosagem , Purinas/efeitos adversos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos Retrospectivos , Tailândia/epidemiologia , Idoso , Receptor ErbB-2/metabolismo , Adulto , Receptores de Estrogênio/metabolismo , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/uso terapêutico , Receptores de Progesterona/metabolismo , Intervalo Livre de Progressão
8.
Eur J Drug Metab Pharmacokinet ; 49(5): 631-644, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39105991

RESUMO

BACKGROUND AND OBJECTIVES: Numerous clinical concerns have been expressed regarding the potential worsening of cyclin-dependent kinase 4/6 inhibitor effects in breast cancer patients because of co-administration of proton pump inhibitors. Hence, this study evaluated the effects of proton pump inhibitors on the pharmacokinetics of palbociclib and ribociclib in terms of  cytochrome P450 (CYP) 3A4 and P-glycoprotein involvement. METHODS: The effects of omeprazole and rabeprazole on drug metabolism and efflux of these drugs were investigated using molecular docking, metabolic stability assay in rat liver microsomes, human recombinant CYP3A4 (rCYP3A4) enzymes, and Caco-2 cell monolayers, and in vivo pharmacokinetics with omeprazole and rabeprazole in (5 and 10 mg/kg) 30 min and 7 days before orally dosing palbociclib and ribociclib (10 mg/kg). RESULTS: Omeprazole and rabeprazole inhibited CYP3A4 enzyme activity in rCYP3A4 baculosomes with a 50-60% inhibition at 30 µM. Additionally, both omeprazole and rabeprazole (10 µm) significantly reduced the P-glycoprotein-mediated drug efflux of palbociclib and ribociclib. The 7-day pretreatment of omeprazole at a dose of 10 mg/kg resulted in 24% and 26% reductions in palbociclib's mean maximum plasma concentration) Cmax and area under the plasma concentration-time curve (AUC0-24 h), respectively. Palbociclib's pharmacokinetics were not significantly altered by the pretreatment with rabeprazole; however, ribociclib pharmacokinetics exhibited an 83.94% increase in AUC0-24 h. CONCLUSION: The findings indicate that long-term treatment with therapeutic doses of both omeprazole and rabeprazole can alter the pharmacokinetics of palbociclib and ribociclib. The co-administration of rabeprazole may alter the pharmacokinetics of palbociclib and ribociclib via CYP enzyme and P-glycoprotein inhibition.


Assuntos
Aminopiridinas , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Citocromo P-450 CYP3A , Interações Medicamentosas , Microssomos Hepáticos , Omeprazol , Piperazinas , Inibidores da Bomba de Prótons , Purinas , Piridinas , Rabeprazol , Animais , Inibidores da Bomba de Prótons/farmacologia , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/farmacocinética , Piperazinas/farmacocinética , Piperazinas/farmacologia , Piperazinas/administração & dosagem , Humanos , Purinas/farmacocinética , Purinas/farmacologia , Ratos , Piridinas/farmacocinética , Piridinas/farmacologia , Piridinas/administração & dosagem , Rabeprazol/farmacologia , Rabeprazol/administração & dosagem , Rabeprazol/farmacocinética , Citocromo P-450 CYP3A/metabolismo , Omeprazol/farmacologia , Omeprazol/farmacocinética , Omeprazol/administração & dosagem , Masculino , Células CACO-2 , Aminopiridinas/farmacocinética , Aminopiridinas/farmacologia , Aminopiridinas/administração & dosagem , Microssomos Hepáticos/metabolismo , Microssomos Hepáticos/efeitos dos fármacos , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Ratos Sprague-Dawley , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/administração & dosagem , Fígado/metabolismo , Fígado/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo
9.
J Manag Care Spec Pharm ; 30(9): 942-953, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39213142

RESUMO

BACKGROUND: Abemaciclib was newly approved for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) high-risk early breast cancer (EBC). Clinical guidelines recommended abemaciclib as the first-line treatment for HR+/ HER2- EBC (early use) or HR+/ HER2- metastatic breast cancer (MBC) (delayed use). OBJECTIVE: To compare the cost-effectiveness of early vs delayed use of abemaciclib for treatment of HR+/HER2- high-risk EBC. Early use was defined as combined abemaciclib and endocrine therapy as first-line therapy for EBC, followed by treatment with fulvestrant for MBC. Delayed use was defined as endocrine therapy for EBC, followed by combined abemaciclib and fulvestrant therapy for MBC. METHODS: A 5-state model was developed to estimate lifetime costs, life-years (LYs), and quality-adjusted life-years (QALYs) of hypothetical patients with HR+/ HER2- EBC from a third-party US payer's perspective. Key clinical and safety data were derived from the monarchE and MONARCH 2 clinical trials. Costs, utilities, and disutility values of adverse events were obtained from the literature. We calculated the incremental cost-effectiveness ratio (ICER) of early vs delayed abemaciclib use and compared it with a willingness-to-pay (WTP) threshold of $100,000 per LY or QALY. Deterministic and probabilistic sensitivity analyses (PSAs) were performed to test the robustness of the base-case model. RESULTS: Base-case analysis showed early use yielded 21.08 LYs and 17.93 QALYs for $586,213 and delayed use yielded 11.14 LYs and 9.38 QALYs for $157,576. The ICER of early vs delayed use was $43,136/LY and $50,104/QALY, which was cost-effective at the WTP threshold of $100,000. The PSA result indicated that a 94.6% likelihood of early use (vs delayed use) was cost-effective at the WTP threshold of $100,000 per QALY. CONCLUSIONS: This study suggests that giving abemaciclib in the early stage rather than waiting until patients develop metastatic disease (current standard of care in MBC) is a cost-effective strategy.


Assuntos
Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Benzimidazóis , Neoplasias da Mama , Análise Custo-Benefício , Anos de Vida Ajustados por Qualidade de Vida , Receptor ErbB-2 , Humanos , Benzimidazóis/economia , Benzimidazóis/uso terapêutico , Benzimidazóis/administração & dosagem , Aminopiridinas/economia , Aminopiridinas/uso terapêutico , Aminopiridinas/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
10.
Anticancer Drugs ; 35(9): 867-871, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39008537

RESUMO

Metastatic spread to the central nervous system (CNS) is frequent in anaplastic lymphoma kinase ( ALK )-rearranged non-small cell lung cancer (NSCLC) and has an important impact on patient prognosis and quality of life. Leptomeningeal involvement may occur in up to 10% of cases of ALK-positive NSCLC. Lorlatinib is a third-generation ALK inhibitor that has excellent CNS penetrability and demonstrated its efficacy both in pretreated and treatment-naive patients. Herein, we present the case of a 34-year-old patient diagnosed with stage IV ALK-rearranged NSCLC who received two lines of ALK inhibitors (crizotinib followed by alectinib) and several courses of brain stereotactic ablative radiotherapy until leptomeningeal involvement was detected. Third-line lorlatinib was then administered, and 2 months later encephalic MRI documented complete regression of the leptomeningeal involvement that is still maintained after 36 months while treatment with lorlatinib is still ongoing with good tolerability. To the best of our knowledge, this is the longer intracranial response reported in the literature, underlining the importance of the most appropriate choice of systemic treatments and their integration with loco-regional approaches to improve outcomes.


Assuntos
Aminopiridinas , Carcinoma Pulmonar de Células não Pequenas , Lactamas , Neoplasias Pulmonares , Pirazóis , Humanos , Lactamas/uso terapêutico , Adulto , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Aminopiridinas/uso terapêutico , Aminopiridinas/administração & dosagem , Pirazóis/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Lactamas Macrocíclicas/uso terapêutico , Masculino , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Quinase do Linfoma Anaplásico/genética
11.
Future Oncol ; 20(28): 2037-2048, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39023253

RESUMO

WHAT IS THIS SUMMARY ABOUT?: This article summarizes the most recent results of the monarchE study. This study was completed in participants with a type of breast cancer called HR+, HER2-, node-positive, high-risk early breast cancer. In this study, abemaciclib, a non-chemotherapy treatment, was administered with standard of care endocrine therapy after curative surgery. Most participants had received prior chemotherapy and/or radiotherapy. The study investigated if abemaciclib helped participants live longer without their cancer returning compared with participants who only received standard of care endocrine therapy. The study participants were assigned to 1 of 2 treatment groups. Participants in Group A were assigned to receive standard of care endocrine therapy with abemaciclib for 2 years, followed by endocrine therapy for a total of at least 5 years. Participants in Group B were assigned to receive standard of care endocrine therapy only for at least 5 years. The effect of treatment was compared between these 2 groups. WHAT WERE THE RESULTS?: Overall, the results showed that the cancer was 34% less likely to come back after surgery in the participants in Group A (abemaciclib plus endocrine therapy) compared with those in Group B (endocrine therapy only). At 4 years since the start of the study treatment, more participants who received the combination of abemaciclib plus endocrine therapy remained free of cancer compared with participants who received endocrine therapy alone (86% versus 79%). Participants who received abemaciclib plus endocrine therapy had more side effects than those who received endocrine therapy alone, but most of these effects were mild to moderate and reversible upon the end of therapy. The most common side effects in the abemaciclib group were diarrhea, infections, low number of white blood cells, and tiredness. WHAT DO THE RESULTS MEAN?: This study found that administering abemaciclib in combination with standard endocrine therapy after curative breast surgery helped lower the risk of cancer returning in people with HR+, HER2-, node-positive, high-risk early breast cancer. Abemaciclib is a new treatment option for people with this diagnosis. People with high-risk early breast cancer should always talk to their doctors and nurses before making any decisions about their treatment.Clinical Trial Registration: NCT03155997 (monarchE study).


Assuntos
Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Benzimidazóis , Neoplasias da Mama , Receptor ErbB-2 , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Feminino , Benzimidazóis/administração & dosagem , Benzimidazóis/uso terapêutico , Aminopiridinas/administração & dosagem , Aminopiridinas/uso terapêutico , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Receptores de Estrogênio/metabolismo , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Pessoa de Meia-Idade , Receptores de Progesterona/metabolismo , Adulto , Resultado do Tratamento , Idoso , Estadiamento de Neoplasias
12.
Front Immunol ; 15: 1415597, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39040100

RESUMO

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by hyperinflammation and organ failure, with a high mortality rate. Current first-line treatments for adult patients have limited efficacy and significant toxicity. The novel selective histone deacetylase inhibitor (HDACi), chidamide, has shown promise in preclinical studies for the potential treatment of HLH. Methods: An open-label, single-center study was conducted to evaluate the efficacy and safety of chidamide in combination with etoposide and glucocorticoids for the treatment of HLH in adult patients. Seventeen patients who fulfilled at least five of the eight HLH-2004 criteria were enrolled and treated with the combination therapy. The primary outcome was overall response rate (ORR), and secondary outcomes included survival, safety and tolerability, and changes in laboratory indicators. Results: A total of 17 HLH patients who met the inclusion criteria were enrolled in this study, with a male to female ratio of 1.8:1. The age range at enrollment was 31 to 71 years old, with a median age of 52 years old. The ORR was 76.5% (13/17 patients), with a complete response (CR) rate of 17.6% (3/17 patients) and a partial response (PR) rate of 58.8% (10/17 patients). The median overall survival (OS) was not achieved, with OS at 6 months and 12 months being 81% and 65%, respectively. The median progression free survival (PFS) was not achieved, with PFS at 6 months and 12 months being 68% and 55%, respectively. Hematologic toxicities is the most common. Safety profile was favorable, with very few cases of grade 3/4 toxicities observed. The results showed that the levels of sCD25, platelets, aspartate aminotransferase, lactate dehydrogenase, and albumin in these patients were significantly improved 3 weeks after treatment. Conclusion: The addition of chidamide to etoposide and glucocorticoids may be a promising new treatment option for patients with HLH, with a high ORR, manageable safety profile, and significant improvement in laboratory indicators. Further research is needed to confirm these findings and determine the optimal dosing and duration of therapy.


Assuntos
Aminopiridinas , Benzamidas , Etoposídeo , Glucocorticoides , Linfo-Histiocitose Hemofagocítica , Humanos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Masculino , Feminino , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/mortalidade , Adulto , Pessoa de Meia-Idade , Benzamidas/administração & dosagem , Benzamidas/efeitos adversos , Benzamidas/uso terapêutico , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Glucocorticoides/efeitos adversos , Aminopiridinas/administração & dosagem , Aminopiridinas/efeitos adversos , Aminopiridinas/uso terapêutico , Resultado do Tratamento , Idoso , Quimioterapia Combinada , Inibidores de Histona Desacetilases/uso terapêutico , Inibidores de Histona Desacetilases/efeitos adversos , Inibidores de Histona Desacetilases/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
13.
J Coll Physicians Surg Pak ; 34(7): 851-853, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38978255

RESUMO

The aim of this study is to share real-life data on the increase in creatinine due to CDK 4/6 inhibitor treatment and patients diagnosed with HR+/HER2-MBC and treated with ribociclib or palbociclib combined with ET were included in the study. While creatinine increase was observed in 17.9% (n = 19) of the 106 patients in the study population, 8.5% (n = 9) had Grade 1, 8.5% (n = 8) had Grade 2, and % 0.9 (n = 1) had Grade 3 creatinine elevation. The increase in creatinine occurred in 25% (n = 12) of ribociclib users and 12.1% (n = 7) of palbociclib users. No patient required a dose reduction or discontinuation of treatment due to elevated creatinine. Of the patients with high creatinine levels, 36.8% (n = 7) were over 65 years of age. Those with multiple comorbidities, blood urea nitrogen (BUN) >13.5 mg/dl, creatinine >0.66 mg/dl, BUN/creatinine ratio >19.95, glomerular filtration rate (GFR) >96.05 ml/min, and uric acid >4.69mg/dl. It was observed that the increase in the creatinine level was statistically significant (p <0.001). In conclusion, this study revealed that the increase in the serum creatinine secondary to ribociclib and palbociclib treatments is associated with kidney function tests and the number of concomitant diseases. Key Words: CDK 4/6 inhibitor, Creatinine elevation, Palbociclib, Ribociclib.


Assuntos
Aminopiridinas , Creatinina , Quinase 4 Dependente de Ciclina , Piperazinas , Purinas , Piridinas , Humanos , Purinas/efeitos adversos , Purinas/administração & dosagem , Purinas/uso terapêutico , Creatinina/sangue , Piperazinas/efeitos adversos , Piperazinas/administração & dosagem , Piperazinas/uso terapêutico , Aminopiridinas/efeitos adversos , Aminopiridinas/administração & dosagem , Aminopiridinas/uso terapêutico , Feminino , Piridinas/efeitos adversos , Piridinas/administração & dosagem , Pessoa de Meia-Idade , Idoso , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Neoplasias da Mama/tratamento farmacológico , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Adulto , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Masculino
14.
JCO Glob Oncol ; 10: e2300433, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39024528

RESUMO

PURPOSE: Incorporating adjuvant cyclin-dependent kinase (CDK) 4/6 inhibitors abemaciclib and ribociclib along with endocrine therapy has been shown to improve invasive disease-free survival (iDFS) for hormone receptor-positive (HR+) human epidermal receptor 2-negative (HER2-) early breast cancer (EBC). This study assesses the cost-effectiveness of this strategy, along with adjuvant aromatase inhibitors from an Indian perspective. METHODS: A Markov chain model evaluated the cost-effectiveness of abemaciclib and ribociclib with letrozole compared with letrozole alone for HR+/HER2- EBC from a payer perspective in India. Key measures included lifetime quality-adjusted life-years (QALY), life-years (LY), and total costs. This study explores two scenarios for effectiveness: a best-case (BC) scenario, where the benefit of CDK4/6 inhibitors in improving iDFS lasts a lifetime, and a worst-case (WC) scenario, where benefits disappear after 5 years. Probabilistic sensitivity analyses (PSA) were used to account for simulation uncertainty. RESULTS: In the BC scenario, abemaciclib added 2.17 QALY and 4.96 LY, incurring ₹2,317,957.7 ($27,756.65 in US dollars [USD]) in additional costs. However, the incremental cost-effectiveness ratio (ICER) for abemaciclib exceeded India's willingness-to-pay threshold in the BC and WC scenarios. In the BC scenario, ribociclib added 0.98 QALY and 2.58 LY with added costs of ₹1,711,504.32 ($20,494.6 USD). The ICER for ribociclib also surpassed India's threshold in both scenarios. PSA showed that neither drug was cost-effective at the current market prices in either BC/WC scenario. The cost of abemaciclib and ribociclib needs to be reduced by at least 78.61% and 87.19%, respectively, to be cost-effective in the BC scenario. CONCLUSION: The combination of adjuvant abemaciclib or ribociclib with letrozole is not cost-effective for HR+/HER2- EBC in India in either the BC or WC scenario.


Assuntos
Aminopiridinas , Benzimidazóis , Neoplasias da Mama , Análise Custo-Benefício , Purinas , Humanos , Aminopiridinas/economia , Aminopiridinas/administração & dosagem , Aminopiridinas/uso terapêutico , Benzimidazóis/economia , Benzimidazóis/administração & dosagem , Benzimidazóis/uso terapêutico , Purinas/economia , Purinas/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/economia , Feminino , Índia , Quimioterapia Adjuvante/economia , Quimioterapia Adjuvante/métodos , Anos de Vida Ajustados por Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cadeias de Markov , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
15.
Support Care Cancer ; 32(8): 492, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976108

RESUMO

OBJECTIVE: We aimed to evaluate cardiac safety profile of ribociclib with 24-h rhythm Holter ECG. MATERIAL AND METHOD: Forty-two female metastatic breast cancer patients were included in the study. Rhythm Holter ECG was performed before starting treatment with ribociclib and after 3 months of the treatment initiation. RESULTS: The mean age of the patients was 56.36 ± 12.73. 52.4% (n = 22) of the patients were using ribociclib in combination with fulvestrant and 47.6% (n = 20) with aromatase inhibitors. None of the patients developed cardiotoxicity. When the rhythm Holter results before and in third month of the treatment were compared, there was no statistically significant difference. CONCLUSION: This is the first study evaluating effects of ribociclib treatment on cardiac rhythm with Holter ECG. The findings suggested ribociclib has a low risk of causing early cardiotoxicity.


Assuntos
Aminopiridinas , Neoplasias da Mama , Eletrocardiografia Ambulatorial , Purinas , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/tratamento farmacológico , Eletrocardiografia Ambulatorial/métodos , Purinas/efeitos adversos , Purinas/administração & dosagem , Idoso , Aminopiridinas/efeitos adversos , Aminopiridinas/administração & dosagem , Adulto , Cardiotoxicidade/etiologia , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
16.
Int J Mol Sci ; 25(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39000513

RESUMO

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, including abemaciclib, have been approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced, and metastatic breast cancer. Despite the high therapeutic efficacy of CDK4/6 inhibitors, they are associated with various adverse effects, including potentially fatal interstitial lung disease. Therefore, a combination of CDK4/6 inhibitors with letrozole or fulvestrant has been attempted but has demonstrated limitations in reducing adverse effects, highlighting the need to develop new combination therapies. This study proposes a combination strategy using CDK4/6 inhibitors and tricyclic antidepressants to enhance the therapeutic outcomes of these inhibitors while reducing their side effects. The therapeutic efficacies of abemaciclib and desipramine were tested in different cancer cell lines (H460, MCF7, and HCT-116). The antitumor effects of the combined abemaciclib and desipramine treatment were evaluated in a xenograft colon tumor model. In vitro cell studies have shown the synergistic anticancer effects of combination therapy in the HCT-116 cell line. The combination treatment significantly reduced tumor size compared with control or single treatment without causing apparent toxicity to normal tissues. Although additional in vivo studies are necessary, this study suggests that the combination therapy of abemaciclib and desipramine may represent a novel therapeutic approach for treating solid tumors.


Assuntos
Aminopiridinas , Benzimidazóis , Desipramina , Sinergismo Farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Benzimidazóis/farmacologia , Benzimidazóis/administração & dosagem , Aminopiridinas/farmacologia , Aminopiridinas/administração & dosagem , Animais , Camundongos , Desipramina/farmacologia , Linhagem Celular Tumoral , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/metabolismo , Proliferação de Células/efeitos dos fármacos , Camundongos Nus , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/metabolismo , Células MCF-7 , Células HCT116 , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Camundongos Endogâmicos BALB C
17.
Ann Hematol ; 103(8): 3083-3093, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38900303

RESUMO

This study aimed to evaluate the efficacy and safety of chidamide (Chi) combined with a modified Busulfan-Cyclophosphamide (mBuCy) conditioning regimen for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twenty-two patients received chidamide combined with mBuCy conditioning regimen (Chi group). A matched-pair control (CON) group of 44 patients (matched 1:2) received mBuCy only in the same period. The leukemia-free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse-related mortality (NRM) were evaluated. Patients in the Chi group were associated with lower 2-year CIR (19.0 vs. 41.4%, P = 0.030), better 2-year LFS (76.1 vs. 48.1%, P = 0.014), and had no significant difference in 2-year OS (80.5 vs. 66.4%, P = 0.088). Patients with minimal residual disease (MRD) positive before HSCT in the Chi group exhibited an advantage in 2-year LFS and a trend towards better 2-year OS (75.0 vs. 10.2%, P = 0.048; 75.0 vs. 11.4%, P = 0.060, respectively). Multivariable analysis showed that the chidamide intensified regimen was independently associated with better LFS (HR 0.23; 95%CI, 0.08-0.63; P = 0.004), and showed no significant impact with OS for all patients (HR 0.34, 95%CI, 0.11-1.07; P = 0.064). The cumulative incidence rates of grade II-IV aGVHD were similar (36.4 vs. 38.6%, P = 0.858). 20 patients in Chi group evinced an elevation in γ-glutamyltransferase, as compared to the mBuCy group (90.9 vs. 65.9%, P = 0.029). No transplantation-related mortality was documented within the first 100 days after transplantation. The results demonstrate that the chidamide intensified regimen may be an effective and acceptable safety option for T-ALL/LBL undergoing allo-HSCT, and further validation is needed.


Assuntos
Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Ciclofosfamida , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Condicionamento Pré-Transplante , Humanos , Masculino , Feminino , Condicionamento Pré-Transplante/métodos , Adulto , Aminopiridinas/administração & dosagem , Aminopiridinas/uso terapêutico , Adolescente , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Benzamidas/administração & dosagem , Benzamidas/uso terapêutico , Adulto Jovem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bussulfano/administração & dosagem , Bussulfano/uso terapêutico , Taxa de Sobrevida , Transplante Homólogo , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/mortalidade , Intervalo Livre de Doença , Estudos Retrospectivos , Aloenxertos
20.
Future Oncol ; 20(29): 2179-2188, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38861285

RESUMO

Aim: To understand the real-world use of abemaciclib in Japanese patients with early breast cancer (EBC).Methods: This retrospective observational study was conducted using a Japanese administrative claims database in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative EBC who received abemaciclib adjuvant therapy from December 2021-March 2023. Patient characteristics and treatment patterns were summarized.Results: Among 374 patients, 38.2, 51.6 and 63.4% patients received neoadjuvant chemotherapy, adjuvant chemotherapy and radiotherapy, respectively; 13.1% were chemotherapy naive. Tamoxifen (37.7%), letrozole (35.6%), anastrozole (24.3%) were the commonly prescribed concomitant adjuvant endocrine therapies. Abemaciclib dose reductions were observed in 42.0% patients.Conclusion: Use of abemaciclib for treatment of high-risk EBC was described, which could help inform patient selection and treatment patterns.


Abemaciclib (150 mg twice daily) is prescribed with hormonal therapy for the treatment of early breast cancer (EBC) with high risk of recurrence. We used a big database from Japan that has anonymized information about 44 million patients from 480 hospitals. We aim to describe the characteristics of patients with EBC who receive abemaciclib and their treatment patterns in Japan.We included 374 patients with EBC who had breast cancer surgery and were prescribed abemaciclib with hormonal therapy between December 2021 and March 2023. The median age of patients is 54 years, almost all (99.2%) are female. The most commonly prescribed hormonal therapy with abemaciclib is tamoxifen (37.7%), letrozole (35.6%) and anastrozole (24.3%).Of the 374 patients who were prescribed abemaciclib, 38.2% patients received chemotherapy before surgery, 51.6% received chemotherapy after surgery and 63.4% received radiation therapy after surgery; whereas, 13.1% received no perioperative chemotherapy before abemaciclib therapy. Around 42% of patients reduced their dose from starting dose of abemaciclib. Higher proportion of older patients and patients with low body weight, had dose reduction. Majority of the patients are prescribed either an antidiarrheal agent or probiotic within a day of starting abemaciclib.This is the first study describing patient characteristics and treatment patterns of Japanese patients who are prescribed abemaciclib in the clinical practice. The results will help understand who can benefit from abemaciclib, and to choose the most appropriate patients to receive abemaciclib for the treatment of EBC.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Estudos Retrospectivos , Pessoa de Meia-Idade , Japão , Idoso , Benzimidazóis/uso terapêutico , Benzimidazóis/administração & dosagem , Adulto , Aminopiridinas/uso terapêutico , Aminopiridinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tamoxifeno/uso terapêutico , Tamoxifeno/administração & dosagem , Anastrozol/uso terapêutico , Anastrozol/administração & dosagem , Receptor ErbB-2/metabolismo
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