RESUMEN
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.
Asunto(s)
Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Letrozol , Posmenopausia , Purinas , Receptor ErbB-2 , Receptores de Estrógenos , Humanos , Aminopiridinas/administración & dosificación , Aminopiridinas/uso terapéutico , Aminopiridinas/efectos adversos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Purinas/administración & dosificación , Purinas/efectos adversos , Persona de Mediana Edad , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Receptores de Estrógenos/metabolismo , Letrozol/administración & dosificación , Letrozol/uso terapéutico , Adulto , China , Anciano , Receptores de Progesterona/metabolismo , Premenopausia , Supervivencia sin Progresión , Goserelina/administración & dosificación , Goserelina/uso terapéutico , Inhibidores de la Aromatasa/administración & dosificación , Inhibidores de la Aromatasa/uso terapéutico , Pueblos del Este de AsiaRESUMEN
PURPOSE: To assess the efficacy and safety of apalutamide plus goserelin for androgen receptor (AR)-positive unresectable or recurrent/metastatic salivary gland carcinoma. PATIENTS AND METHODS: This trial was an open-label, single-arm, multicenter phase II study. Patients with histologically confirmed unresectable or recurrent/metastatic salivary gland carcinoma with AR expression were included. The primary endpoint was the overall response rate (ORR) according to RECIST v1.1 by an independent central radiology review in the first 24 response-evaluable (RE) patients who had been observed at least 24 weeks from study initiation (primary RE patients). The efficacy was to be declared when at least 8 of the 24 primary RE patients responded. RESULTS: A total of 31 patients were enrolled. In the first 24 primary RE patients with a median follow-up of 7.4 months, confirmed ORR by independent central radiology review was 25.0% [6/24 patients; 95% confidence interval, 9.8%-46.7%; P = 0.11 (one-sided)], which did not meet the predefined criteria of efficacy. Clinical benefit rate (ORR + rate of stable disease for at least 24 weeks) and median progression-free survival were 50.0% and 7.4 months, respectively. Both median duration of response and overall survival were not reached. Exploratory analyses showed a better ORR of 54.5% (6/11) in patients with AR positivity ≥70% and no history of prior systemic therapy. Grade 3 or higher treatment-emergent adverse events were reported in 35.5% (11/31), which included skin rash, anemia, leukopenia, and cancer pain. CONCLUSIONS: Although this study did not meet the predefined efficacy criteria, apalutamide plus goserelin showed clinically meaningful efficacy in a subset of patients with AR-positive salivary gland carcinoma and safety consistent with prior experience in prostate cancer.
Asunto(s)
Goserelina , Receptores Androgénicos , Neoplasias de las Glándulas Salivales , Tiohidantoínas , Humanos , Masculino , Persona de Mediana Edad , Femenino , Anciano , Neoplasias de las Glándulas Salivales/tratamiento farmacológico , Neoplasias de las Glándulas Salivales/patología , Neoplasias de las Glándulas Salivales/metabolismo , Neoplasias de las Glándulas Salivales/mortalidad , Receptores Androgénicos/metabolismo , Tiohidantoínas/administración & dosificación , Tiohidantoínas/uso terapéutico , Tiohidantoínas/efectos adversos , Adulto , Goserelina/administración & dosificación , Goserelina/uso terapéutico , Goserelina/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano de 80 o más Años , Resultado del Tratamiento , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patologíaRESUMEN
PURPOSE: This study evaluated the effectiveness of ovarian function suppression (OFS) of various gonadotropin-releasing hormone agonists (GnRHa) combined with aromatase inhibitors (AI) in premenopausal patients with hormone receptor-positive (HR-positive) breast cancer. Potential risk factors associated with insufficient OFS were analyzed. PATIENTS AND METHODS: Premenopausal HR-positive breast cancer patients who had received AI with GnRHa were studied retrospectively. Patients were divided into different groups according to monthly or trimonthly GnRHa schedules they received, and the effectiveness of OFS was compared between groups. Insufficient OFS was defined as at least one instance of estradiol ≥ 30 pg/ml. Patient data was gathered from medical records for this comparison. RESULTS: Of the 264 patients enrolled in this study, 117 were administered 3.6 mg of goserelin monthly (goserelin 1 M group), 63 received 3.75 mg of leuprorelin monthly (leuprorelin 1 M group) and 84 were given 11.25 mg of leuprorelin every three months (leuprorelin 3 M group). Overall, 7.20% experienced insufficient OFS. The incidence rates in the three GnRHa depot groups were 7.69%, 6.35%, and 7.14%, respectively, without a significant statistical difference (P = 0.900). Notably, younger patients exhibited a higher likelihood of insufficient OFS [OR = 0.900, 95%CI (0.824-0.982), P = 0.018]. CONCLUSION: Insufficient OFS remains a concern during GnRHa and AI treatment. The effectiveness of the three GnRHa depots commonly used in China seems comparable. Younger patients face a heightened risk of insufficient OFS.
Asunto(s)
Inhibidores de la Aromatasa , Neoplasias de la Mama , Hormona Liberadora de Gonadotropina , Premenopausia , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Adulto , Estudios Retrospectivos , Hormona Liberadora de Gonadotropina/agonistas , Persona de Mediana Edad , Inhibidores de la Aromatasa/uso terapéutico , Ovario/efectos de los fármacos , Ovario/metabolismo , Antineoplásicos Hormonales/uso terapéutico , Resultado del Tratamiento , Receptores de Estrógenos/metabolismo , Goserelina/uso terapéutico , Goserelina/administración & dosificación , Leuprolida/uso terapéutico , Leuprolida/administración & dosificación , Receptores de Progesterona/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
OBJECTIVES: Metastatic prostate cancer is the most common malignant cancer and the second leading cause of death due to various types of cancer among men after lung cancer. This study aimed to analyze the cost-effectiveness of triptorelin, goserelin, and leuprolide in the treatment of the patients with metastatic prostate cancer from the societal perspective in Iran in 2020. METHODS: This is a cost-effectiveness study in which a 20-year Markov transition modeling was applied. In this study, local cost and quality-of-life data of each health state were gathered from cohort of patients. The TreeAge pro 2020 and Microsoft Excel 2016 software were used to simulate cost-effectiveness of each treatment in the long term. The one-way and probabilistic sensitivity analyses were also performed to measure robustness of the model outputs. RESULTS: The findings indicated that the mean costs and utility gained over a 20-year horizon for goserelin, triptorelin, and leuprolide treatments were $ 13 539.13 and 6.365 quality-adjusted life-years (QALY), $ 18 124.75 and 6.658 QALY, and $ 26 006.92 and 6.856 QALY, respectively. Goserelin was considered as a superior treatment option, given the estimated incremental cost-effectiveness ratio. The one-way and probabilistic sensitivity analyses confirmed the robustness of the study outcomes. CONCLUSIONS: According to the results of the present study, goserelin was the most effective and cost-effective strategy versus 2 other options. It could be recommended to policy makers of the Iran healthcare system to prioritize it in clinical guidelines and reimbursement policies.
Asunto(s)
Antineoplásicos Hormonales , Goserelina , Leuprolida , Neoplasias de la Próstata , Años de Vida Ajustados por Calidad de Vida , Pamoato de Triptorelina , Anciano , Humanos , Masculino , Persona de Mediana Edad , Antineoplásicos Hormonales/uso terapéutico , Antineoplásicos Hormonales/economía , Análisis de Costo-Efectividad , Goserelina/uso terapéutico , Goserelina/economía , Goserelina/administración & dosificación , Irán , Leuprolida/uso terapéutico , Leuprolida/economía , Leuprolida/administración & dosificación , Cadenas de Markov , Metástasis de la Neoplasia , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/economía , Calidad de Vida , Pamoato de Triptorelina/uso terapéutico , Pamoato de Triptorelina/economía , Pamoato de Triptorelina/administración & dosificaciónRESUMEN
BACKGROUND: Ribociclib has been shown to have a significant overall survival benefit in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Whether this benefit in advanced breast cancer extends to early breast cancer is unclear. METHODS: In this international, open-label, randomized, phase 3 trial, we randomly assigned patients with HR-positive, HER2-negative early breast cancer in a 1:1 ratio to receive ribociclib (at a dose of 400 mg per day for 3 weeks, followed by 1 week off, for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI; letrozole at a dose of 2.5 mg per day or anastrozole at a dose of 1 mg per day for ≥5 years) or an NSAI alone. Premenopausal women and men also received goserelin every 28 days. Eligible patients had anatomical stage II or III breast cancer. Here we report the results of a prespecified interim analysis of invasive disease-free survival, the primary end point; other efficacy and safety results are also reported. Invasive disease-free survival was evaluated with the use of the Kaplan-Meier method. The statistical comparison was made with the use of a stratified log-rank test, with a protocol-specified stopping boundary of a one-sided P-value threshold of 0.0128 for superior efficacy. RESULTS: As of the data-cutoff date for this prespecified interim analysis (January 11, 2023), a total of 426 patients had had invasive disease, recurrence, or death. A significant invasive disease-free survival benefit was seen with ribociclib plus an NSAI as compared with an NSAI alone. At 3 years, invasive disease-free survival was 90.4% with ribociclib plus an NSAI and 87.1% with an NSAI alone (hazard ratio for invasive disease, recurrence, or death, 0.75; 95% confidence interval, 0.62 to 0.91; P = 0.003). Secondary end points - distant disease-free survival and recurrence-free survival - also favored ribociclib plus an NSAI. The 3-year regimen of ribociclib at a 400-mg starting dose plus an NSAI was not associated with any new safety signals. CONCLUSIONS: Ribociclib plus an NSAI significantly improved invasive disease-free survival among patients with HR-positive, HER2-negative stage II or III early breast cancer. (Funded by Novartis; NATALEE ClinicalTrials.gov number, NCT03701334.).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Inhibidores de la Aromatasa , Neoplasias de la Mama , Letrozol , Femenino , Humanos , Aminopiridinas/administración & dosificación , Aminopiridinas/efectos adversos , Aminopiridinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Letrozol/administración & dosificación , Letrozol/efectos adversos , Letrozol/uso terapéutico , Purinas/administración & dosificación , Purinas/efectos adversos , Purinas/uso terapéutico , Receptor ErbB-2/metabolismo , Inhibidores de la Aromatasa/administración & dosificación , Inhibidores de la Aromatasa/efectos adversos , Inhibidores de la Aromatasa/uso terapéutico , Receptores de Estrógenos , Receptores de Progesterona , Goserelina/administración & dosificación , Goserelina/efectos adversos , Goserelina/uso terapéutico , Antineoplásicos Hormonales , MasculinoAsunto(s)
Humanos , Protocolos Clínicos/normas , Endometriosis/cirugía , Endometriosis/diagnóstico , Endometriosis/tratamiento farmacológico , Progestinas/administración & dosificación , Leuprolida/administración & dosificación , Pamoato de Triptorelina/administración & dosificación , Goserelina/administración & dosificación , Laparoscopía/métodos , Anticonceptivos Orales/administración & dosificación , Danazol/administración & dosificaciónRESUMEN
Muestra nuestra experiencia en el tratamiento secuencial y combinado, quirúrgico y médico con análogos del GnRh de depósito (Lupron 3,75), hiperestimulación ovárica controlada con gonadotrofinas HMG-HCG y posterior Second Look laparoscópico con técnica de transferencia intratubaria de gametos. Se evaluó 61 pacientes que consultaron por infertilidad en el Instituto de Ginecología y Fertilidad de Bs. As., entre el 1º de octubre de 1992 y el 30 de diciembre de 1994. En todas ellas se realizó una laparoscopia para el diagnóstico y estadificación de la endometrosis según la clasificación revisada de la Sociedad Americana de Fertilidad, realizándose en el mismo acto los procedimientos quirúrgicos de coagulación, lisis o quistectomía según fuera necesario. Todas las pacientes fueron medicadas con Lupron 3,75 de aplicación mensual durante un período de 6 meses posteriores a la cirugía. Del total de 61 pacientes, 29 (47,5 por ciento) se embarazaron con tratamiento quirúrgico, médico e hiperestimulación ovárica, de las cuales 17 (59 por ciento) lo logró en forma espontánea, 13 (44,8 por ciento) en el primer semestre y 4 (13,7 por ciento) en el segundo semestre postratamiento. Sobre 35 pacientes estimuladas, a partir de los 6 meses de finalizado el Lupron por un período de 3,2 ciclos se embarazaron 12 (41 por ciento). A 10 pacientes se les realizó al cabo de un año de finalizado el tratamiento con análogos un second look laparoscópico con técnica de transferencia intratubaria de gametos, logrando el embarazo en 5 pacientes (50 por ciento). Los resultados obtenidos sugieren que el tratamiento propuesto ha sido útil en este grupo de pacientes, logrando además una adecuada tolerancia y aceptación por parte de las mismas