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1.
Gynecol Oncol ; 164(1): 12-17, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34763937

RESUMEN

OBJECTIVES: We sought to determine the safety and efficacy of the oral androgen receptor antagonist enzalutamide in patients with previously treated, recurrent, AR-positive (AR+) ovarian cancer. METHODS: This was a single-institution phase II study of patients with AR+ ovarian cancer with measurable disease with 1-3 prior lines of chemotherapy; patients were screened for enrollment from 11/2013-7/2018. Following consent, archival tissue was evaluated for AR+. Enrolled patients received daily enzalutamide 160 mg until progression of disease or treatment discontinuation. Adverse events were graded by CTCAE v4.0. Co-primary endpoints were 6-month progression-free survival (PFS6) and overall response rate (ORR) by RECIST 1.1 criteria. RESULTS: During the study period, 160 patients were screened and 59 (45 high-grade serous [HGS] and 14 low-grade serous [LGS]) consented to treatment on study. There was 1 confirmed and 1 unconfirmed partial response. The ORR was 1.7% (90% CI: 0.2-100%). The overall PFS6 rate (as binary) was 22% (90% CI: 15.1-100%). The 6-month PFS rate (as time to event) was 19.8% for HGS patients (90% CI: 12.7-100%) and 38.5% (90% CI: 21.7%-100%) for LGS patients. Grade 3 toxicities occurred in 6 patients (one toxicity (Grade 3 rash) was considered a dose-limiting toxicity). One patient died of cardiac arrest after 42 days on treatment of a cardiac arrest not attributed to study drug. CONCLUSIONS: The study met its primary endpoint, with a PFS6 rate of 22% (n = 13); however, the overall response rate was low. Enzalutamide was well tolerated and may be a potential treatment option in select patients.


Asunto(s)
Benzamidas/uso terapéutico , Cistadenocarcinoma Seroso/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Nitrilos/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Feniltiohidantoína/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas/administración & dosificación , Cistadenocarcinoma Seroso/mortalidad , Cistadenocarcinoma Seroso/patología , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , New York , Nitrilos/administración & dosificación , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Feniltiohidantoína/administración & dosificación , Supervivencia sin Progresión , Receptores Androgénicos/metabolismo
2.
J Immunother Cancer ; 8(1)2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32503949

RESUMEN

BACKGROUND: Immune checkpoint inhibitors (ICIs) to date have demonstrated limited activity in advanced ovarian cancer (OC). Folate receptor alpha (FRα) is overexpressed in the majority of OCs and presents an attractive target for a combination immunotherapy to potentially overcome resistance to ICI in OCs. The current study sought to examine clinical and immunologic responses to TPIV200, a multiepitope FRα vaccine administered with programmed death ligand 1 (PD-L1) inhibitor durvalumab in patients with advanced platinum-resistant OC. METHODS: Following Simon two-stage phase II trial design, 27 patients were enrolled. Treatment was administered in 28-day cycles (intradermal TPIV200 and granulocyte-macrophage colony-stimulating factor (GM-CSF) for 6 cycles and intravenous durvalumab for 12 cycles). Primary endpoints included overall response rate and progression-free survival at 24 weeks. Translational parameters focused on tumor microenvironment, PD-L1 and FRα expression, and peripheral vaccine-specific immune responses. RESULTS: Treatment was well tolerated, with related grade 3 toxicity rate of 18.5%. Increased T cell responses to the majority of peptides were observed in all patients at 6 weeks (p<0.0001). There was one unconfirmed partial response (3.7%) and nine patients had stable disease (33.3%). Clinical benefit was not associated with baseline FRα or PD-L1 expression. One patient with prolonged clinical benefit demonstrated loss of FRα expression and upregulation of PD-L1 in a progressing lesion. Despite the low overall response rate, the median overall survival was 21 months (13.5-∞), with evidence of benefit from postimmunotherapy regimens. CONCLUSIONS: Combination of TPIV200 and durvalumab was safe and elicited robust FRα-specific T cell responses in all patients. Unexpectedly durable survival in this heavily pretreated population highlights the need to investigate the impact of FRα vaccination on the OC biology post-treatment.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Biomarcadores de Tumor/inmunología , Vacunas contra el Cáncer/uso terapéutico , Receptor 1 de Folato/inmunología , Neoplasias Ováricas/tratamiento farmacológico , Microambiente Tumoral/inmunología , Adenocarcinoma de Células Claras/tratamiento farmacológico , Adenocarcinoma de Células Claras/inmunología , Adenocarcinoma de Células Claras/patología , Adulto , Anciano , Antineoplásicos Inmunológicos/uso terapéutico , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/inmunología , Cistadenocarcinoma Seroso/patología , Quimioterapia Combinada , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/inmunología , Neoplasias Endometriales/patología , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Ensayos Clínicos Controlados no Aleatorios como Asunto , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Pronóstico , Tasa de Supervivencia , Resultado del Tratamiento
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