Cargando…
Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy
BACKGROUND: In Study 19, maintenance monotherapy with olaparib significantly prolonged progression-free survival vs placebo in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer. METHODS: Study 19 was a randomised, placebo-controlled, Phase II trial enrolling 265 patients w...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219499/ https://www.ncbi.nlm.nih.gov/pubmed/30353045 http://dx.doi.org/10.1038/s41416-018-0271-y |
_version_ | 1783368664790073344 |
---|---|
author | Friedlander, Michael Matulonis, Ursula Gourley, Charlie du Bois, Andreas Vergote, Ignace Rustin, Gordon Scott, Clare Meier, Werner Shapira-Frommer, Ronnie Safra, Tamar Matei, Daniela Shirinkin, Vadim Selle, Frédéric Fielding, Anitra Lowe, Elizabeth S. McMurtry, Emma L. Spencer, Stuart Rowe, Philip Mann, Helen Parry, David Ledermann, Jonathan |
author_facet | Friedlander, Michael Matulonis, Ursula Gourley, Charlie du Bois, Andreas Vergote, Ignace Rustin, Gordon Scott, Clare Meier, Werner Shapira-Frommer, Ronnie Safra, Tamar Matei, Daniela Shirinkin, Vadim Selle, Frédéric Fielding, Anitra Lowe, Elizabeth S. McMurtry, Emma L. Spencer, Stuart Rowe, Philip Mann, Helen Parry, David Ledermann, Jonathan |
author_sort | Friedlander, Michael |
collection | PubMed |
description | BACKGROUND: In Study 19, maintenance monotherapy with olaparib significantly prolonged progression-free survival vs placebo in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer. METHODS: Study 19 was a randomised, placebo-controlled, Phase II trial enrolling 265 patients who had received at least two platinum-based chemotherapy regimens and were in complete or partial response to their most recent regimen. Patients were randomised to olaparib (capsules; 400 mg bid) or placebo. We present long-term safety and final mature overall survival (OS; 79% maturity) data, from the last data cut-off (9 May 2016). RESULTS: Thirty-two patients (24%) received maintenance olaparib for over 2 years; 15 (11%) did so for over 6 years. No new tolerability signals were identified with long-term treatment and adverse events were generally low grade. The incidence of discontinuations due to adverse events was low (6%). An apparent OS advantage was observed with olaparib vs placebo (hazard ratio 0.73, 95% confidence interval 0.55‒0.95, P = 0.02138) irrespective of BRCA1/2 mutation status, although the predefined threshold for statistical significance was not met. CONCLUSIONS: Study 19 showed a favourable final OS result irrespective of BRCA1/2 mutation status and unprecedented long-term benefit with maintenance olaparib for a subset of platinum-sensitive, recurrent ovarian cancer patients. |
format | Online Article Text |
id | pubmed-6219499 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-62194992020-01-16 Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy Friedlander, Michael Matulonis, Ursula Gourley, Charlie du Bois, Andreas Vergote, Ignace Rustin, Gordon Scott, Clare Meier, Werner Shapira-Frommer, Ronnie Safra, Tamar Matei, Daniela Shirinkin, Vadim Selle, Frédéric Fielding, Anitra Lowe, Elizabeth S. McMurtry, Emma L. Spencer, Stuart Rowe, Philip Mann, Helen Parry, David Ledermann, Jonathan Br J Cancer Article BACKGROUND: In Study 19, maintenance monotherapy with olaparib significantly prolonged progression-free survival vs placebo in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer. METHODS: Study 19 was a randomised, placebo-controlled, Phase II trial enrolling 265 patients who had received at least two platinum-based chemotherapy regimens and were in complete or partial response to their most recent regimen. Patients were randomised to olaparib (capsules; 400 mg bid) or placebo. We present long-term safety and final mature overall survival (OS; 79% maturity) data, from the last data cut-off (9 May 2016). RESULTS: Thirty-two patients (24%) received maintenance olaparib for over 2 years; 15 (11%) did so for over 6 years. No new tolerability signals were identified with long-term treatment and adverse events were generally low grade. The incidence of discontinuations due to adverse events was low (6%). An apparent OS advantage was observed with olaparib vs placebo (hazard ratio 0.73, 95% confidence interval 0.55‒0.95, P = 0.02138) irrespective of BRCA1/2 mutation status, although the predefined threshold for statistical significance was not met. CONCLUSIONS: Study 19 showed a favourable final OS result irrespective of BRCA1/2 mutation status and unprecedented long-term benefit with maintenance olaparib for a subset of platinum-sensitive, recurrent ovarian cancer patients. Nature Publishing Group UK 2018-10-24 2018-10-30 /pmc/articles/PMC6219499/ /pubmed/30353045 http://dx.doi.org/10.1038/s41416-018-0271-y Text en © The Author(s) 2018 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Friedlander, Michael Matulonis, Ursula Gourley, Charlie du Bois, Andreas Vergote, Ignace Rustin, Gordon Scott, Clare Meier, Werner Shapira-Frommer, Ronnie Safra, Tamar Matei, Daniela Shirinkin, Vadim Selle, Frédéric Fielding, Anitra Lowe, Elizabeth S. McMurtry, Emma L. Spencer, Stuart Rowe, Philip Mann, Helen Parry, David Ledermann, Jonathan Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy |
title | Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy |
title_full | Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy |
title_fullStr | Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy |
title_full_unstemmed | Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy |
title_short | Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy |
title_sort | long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219499/ https://www.ncbi.nlm.nih.gov/pubmed/30353045 http://dx.doi.org/10.1038/s41416-018-0271-y |
work_keys_str_mv | AT friedlandermichael longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT matulonisursula longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT gourleycharlie longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT duboisandreas longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT vergoteignace longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT rustingordon longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT scottclare longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT meierwerner longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT shapirafrommerronnie longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT safratamar longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT mateidaniela longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT shirinkinvadim longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT sellefrederic longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT fieldinganitra longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT loweelizabeths longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT mcmurtryemmal longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT spencerstuart longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT rowephilip longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT mannhelen longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT parrydavid longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy AT ledermannjonathan longtermefficacytolerabilityandoverallsurvivalinpatientswithplatinumsensitiverecurrenthighgradeserousovariancancertreatedwithmaintenanceolaparibcapsulesfollowingresponsetochemotherapy |