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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446804/ https://www.ncbi.nlm.nih.gov/pubmed/34329939 http://dx.doi.org/10.1016/j.esmoop.2021.100212 |
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author | Perez-Fidalgo, J.A. Cortés, A. Guerra, E. García, Y. Iglesias, M. Bohn Sarmiento, U. Calvo García, E. Manso Sánchez, L. Santaballa, A. Oaknin, A. Redondo, A. Rubio, M.J. González-Martín, A. |
author_facet | Perez-Fidalgo, J.A. Cortés, A. Guerra, E. García, Y. Iglesias, M. Bohn Sarmiento, U. Calvo García, E. Manso Sánchez, L. Santaballa, A. Oaknin, A. Redondo, A. Rubio, M.J. González-Martín, A. |
author_sort | Perez-Fidalgo, J.A. |
collection | PubMed |
description | 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) + 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/m(2) (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 PLD–olaparib combination has shown significant activity in PROC regardless of BRCA status. PLD at 30 mg/m(2) is better tolerated in the combination. |
format | Online Article Text |
id | pubmed-8446804 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-84468042021-09-22 Olaparib in combination with pegylated liposomal doxorubicin for platinum-resistant ovarian cancer regardless of BRCA status: a GEICO phase II trial (ROLANDO study) Perez-Fidalgo, J.A. Cortés, A. Guerra, E. García, Y. Iglesias, M. Bohn Sarmiento, U. Calvo García, E. Manso Sánchez, L. Santaballa, A. Oaknin, A. Redondo, A. Rubio, M.J. González-Martín, A. ESMO Open Original Research 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) + 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/m(2) (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 PLD–olaparib combination has shown significant activity in PROC regardless of BRCA status. PLD at 30 mg/m(2) is better tolerated in the combination. Elsevier 2021-07-27 /pmc/articles/PMC8446804/ /pubmed/34329939 http://dx.doi.org/10.1016/j.esmoop.2021.100212 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Perez-Fidalgo, J.A. Cortés, A. Guerra, E. García, Y. Iglesias, M. Bohn Sarmiento, U. Calvo García, E. Manso Sánchez, L. Santaballa, A. Oaknin, A. Redondo, A. Rubio, M.J. González-Martín, A. Olaparib in combination with pegylated liposomal doxorubicin for platinum-resistant ovarian cancer regardless of BRCA status: a GEICO phase II trial (ROLANDO study) |
title | Olaparib in combination with pegylated liposomal doxorubicin for platinum-resistant ovarian cancer regardless of BRCA status: a GEICO phase II trial (ROLANDO study) |
title_full | Olaparib in combination with pegylated liposomal doxorubicin for platinum-resistant ovarian cancer regardless of BRCA status: a GEICO phase II trial (ROLANDO study) |
title_fullStr | Olaparib in combination with pegylated liposomal doxorubicin for platinum-resistant ovarian cancer regardless of BRCA status: a GEICO phase II trial (ROLANDO study) |
title_full_unstemmed | Olaparib in combination with pegylated liposomal doxorubicin for platinum-resistant ovarian cancer regardless of BRCA status: a GEICO phase II trial (ROLANDO study) |
title_short | Olaparib in combination with pegylated liposomal doxorubicin for platinum-resistant ovarian cancer regardless of BRCA status: a GEICO phase II trial (ROLANDO study) |
title_sort | olaparib in combination with pegylated liposomal doxorubicin for platinum-resistant ovarian cancer regardless of brca status: a geico phase ii trial (rolando study) |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446804/ https://www.ncbi.nlm.nih.gov/pubmed/34329939 http://dx.doi.org/10.1016/j.esmoop.2021.100212 |
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