Olaparib in combination with pegylated liposomal doxorubicin for platinum-resistant ovarian cancer regardless of BRCA status: a GEICO phase II trial (ROLANDO study)

Background: There is limited evidence for the benefit of olaparib in platinum-resistant ovarian cancer (PROC) patients with BRCA wild-type tumors. This study investigated whether this combination of a DNA-damaging chemotherapy plus olaparib is effective in PROC regardless BRCA status. Patients and m...

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Detalles Bibliográficos
Autores: Perez-Fidalgo, JA, Cortes, A, Guerra, E, Garcia, Y, Iglesias, M, Sarmiento, UB, Garcia, EC, Sanchez, LM, Santaballa, A, Oaknin, A, Redondo, A, Rubio, MJ, Gonzalez-Martin, A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Institut d'Investigació i Innovació Parc Taulí (I3PT)
Repositorio:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
OAI Identifier:oai:i3pt.fundanetsuite.com:p1980
Acceso en línea:https://i3pt.portalinvestigacion.com/publicaciones/1980
Access Level:acceso abierto
Palabra clave:platinum-resistant recurrent ovarian cancer
PARP inhibitor
olaparib
pegylated liposomal doxorubicin
BRCA wild-type
Descripción
Sumario:Background: There is limited evidence for the benefit of olaparib in platinum-resistant ovarian cancer (PROC) patients with BRCA wild-type tumors. This study investigated whether this combination of a DNA-damaging chemotherapy plus olaparib is effective in PROC regardless BRCA status. Patients and methods: Patients with high-grade serous or endometrioid ovarian carcinoma and one previous PROC recurrence were enrolled regardless of BRCA status. Patients with <= 4 previous lines (up to 5 in BRCA-mut) with at least one previous platinum-sensitive relapse were included; primary PROC was allowed only in case of BRCA-mut. Patients initially received six cycles of olaparib 300 mg b.i.d. (biduum) thorn intravenous pegylated liposomal doxorubicin (PLD) 40 mg/m(2) (PLD40) every 28 days, followed by maintenance with olaparib 300 mg b.i.d. until progression or toxicity. The PLD dose was reduced to 30 mg/m2 (PLD30) due to toxicity. The primary endpoint was progression-free survival (PFS) at 6 months (6m-PFS) by RECIST version 1.1. A proportion of 40% 6m-PFS or more was considered of clinical interest. Results: From 2017 to 2020, 31 PROC patients were included. BRCA mutations were present in 16%. The median of previous lines was 2 (range 1-5). The overall disease control rate was 77% (partial response rate of 29% and stable disease rate of 48%). After a median follow-up of 10 months, the 6m-PFS and median PFS were 47% and 5.8 months, respectively. Grade >= 3 treatment-related adverse events occurred in 74% of patients, with neutropenia/anemia being the most frequent. With PLD30 serious AEs were less frequent than with PLD40 (21% versus 47%, respectively); moreover, PLD30 was associated with less PLD delays (32% versus 38%) and reductions (16% versus 22%). Conclusions: The PLDeolaparib combination has shown significant activity in PROC regardless of BRCA status. PLD at 30 mg/m2 is better tolerated in the combination.