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Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration
PURPOSE: BRCA1 or BRCA2 (BRCA) alterations are common in men with metastatic castration-resistant prostate cancer (mCRPC) and may confer sensitivity to poly(ADP-ribose) polymerase inhibitors. We present results from patients with mCRPC associated with a BRCA alteration treated with rucaparib 600 mg...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Clinical Oncology
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655021/ https://www.ncbi.nlm.nih.gov/pubmed/32795228 http://dx.doi.org/10.1200/JCO.20.01035 |
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author | Abida, Wassim Patnaik, Akash Campbell, David Shapiro, Jeremy Bryce, Alan H. McDermott, Ray Sautois, Brieuc Vogelzang, Nicholas J. Bambury, Richard M. Voog, Eric Zhang, Jingsong Piulats, Josep M. Ryan, Charles J. Merseburger, Axel S. Daugaard, Gedske Heidenreich, Axel Fizazi, Karim Higano, Celestia S. Krieger, Laurence E. Sternberg, Cora N. Watkins, Simon P. Despain, Darrin Simmons, Andrew D. Loehr, Andrea Dowson, Melanie Golsorkhi, Tony Chowdhury, Simon |
author_facet | Abida, Wassim Patnaik, Akash Campbell, David Shapiro, Jeremy Bryce, Alan H. McDermott, Ray Sautois, Brieuc Vogelzang, Nicholas J. Bambury, Richard M. Voog, Eric Zhang, Jingsong Piulats, Josep M. Ryan, Charles J. Merseburger, Axel S. Daugaard, Gedske Heidenreich, Axel Fizazi, Karim Higano, Celestia S. Krieger, Laurence E. Sternberg, Cora N. Watkins, Simon P. Despain, Darrin Simmons, Andrew D. Loehr, Andrea Dowson, Melanie Golsorkhi, Tony Chowdhury, Simon |
author_sort | Abida, Wassim |
collection | PubMed |
description | PURPOSE: BRCA1 or BRCA2 (BRCA) alterations are common in men with metastatic castration-resistant prostate cancer (mCRPC) and may confer sensitivity to poly(ADP-ribose) polymerase inhibitors. We present results from patients with mCRPC associated with a BRCA alteration treated with rucaparib 600 mg twice daily in the phase II TRITON2 study. METHODS: We enrolled patients who progressed after one to two lines of next-generation androgen receptor–directed therapy and one taxane-based chemotherapy for mCRPC. Efficacy and safety populations included patients with a deleterious BRCA alteration who received ≥ 1 dose of rucaparib. Key efficacy end points were objective response rate (ORR; per RECIST/Prostate Cancer Clinical Trials Working Group 3 in patients with measurable disease as assessed by blinded, independent radiology review and by investigators) and locally assessed prostate-specific antigen (PSA) response (≥ 50% decrease from baseline) rate. RESULTS: Efficacy and safety populations included 115 patients with a BRCA alteration with or without measurable disease. Confirmed ORRs per independent radiology review and investigator assessment were 43.5% (95% CI, 31.0% to 56.7%; 27 of 62 patients) and 50.8% (95% CI, 38.1% to 63.4%; 33 of 65 patients), respectively. The confirmed PSA response rate was 54.8% (95% CI, 45.2% to 64.1%; 63 of 115 patients). ORRs were similar for patients with a germline or somatic BRCA alteration and for patients with a BRCA1 or BRCA2 alteration, while a higher PSA response rate was observed in patients with a BRCA2 alteration. The most frequent grade ≥ 3 treatment-emergent adverse event was anemia (25.2%; 29 of 115 patients). CONCLUSION: Rucaparib has antitumor activity in patients with mCRPC and a deleterious BRCA alteration, but with a manageable safety profile consistent with that reported in other solid tumor types. |
format | Online Article Text |
id | pubmed-7655021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society of Clinical Oncology |
record_format | MEDLINE/PubMed |
spelling | pubmed-76550212020-11-12 Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration Abida, Wassim Patnaik, Akash Campbell, David Shapiro, Jeremy Bryce, Alan H. McDermott, Ray Sautois, Brieuc Vogelzang, Nicholas J. Bambury, Richard M. Voog, Eric Zhang, Jingsong Piulats, Josep M. Ryan, Charles J. Merseburger, Axel S. Daugaard, Gedske Heidenreich, Axel Fizazi, Karim Higano, Celestia S. Krieger, Laurence E. Sternberg, Cora N. Watkins, Simon P. Despain, Darrin Simmons, Andrew D. Loehr, Andrea Dowson, Melanie Golsorkhi, Tony Chowdhury, Simon J Clin Oncol RAPID COMMUNICATIONS PURPOSE: BRCA1 or BRCA2 (BRCA) alterations are common in men with metastatic castration-resistant prostate cancer (mCRPC) and may confer sensitivity to poly(ADP-ribose) polymerase inhibitors. We present results from patients with mCRPC associated with a BRCA alteration treated with rucaparib 600 mg twice daily in the phase II TRITON2 study. METHODS: We enrolled patients who progressed after one to two lines of next-generation androgen receptor–directed therapy and one taxane-based chemotherapy for mCRPC. Efficacy and safety populations included patients with a deleterious BRCA alteration who received ≥ 1 dose of rucaparib. Key efficacy end points were objective response rate (ORR; per RECIST/Prostate Cancer Clinical Trials Working Group 3 in patients with measurable disease as assessed by blinded, independent radiology review and by investigators) and locally assessed prostate-specific antigen (PSA) response (≥ 50% decrease from baseline) rate. RESULTS: Efficacy and safety populations included 115 patients with a BRCA alteration with or without measurable disease. Confirmed ORRs per independent radiology review and investigator assessment were 43.5% (95% CI, 31.0% to 56.7%; 27 of 62 patients) and 50.8% (95% CI, 38.1% to 63.4%; 33 of 65 patients), respectively. The confirmed PSA response rate was 54.8% (95% CI, 45.2% to 64.1%; 63 of 115 patients). ORRs were similar for patients with a germline or somatic BRCA alteration and for patients with a BRCA1 or BRCA2 alteration, while a higher PSA response rate was observed in patients with a BRCA2 alteration. The most frequent grade ≥ 3 treatment-emergent adverse event was anemia (25.2%; 29 of 115 patients). CONCLUSION: Rucaparib has antitumor activity in patients with mCRPC and a deleterious BRCA alteration, but with a manageable safety profile consistent with that reported in other solid tumor types. American Society of Clinical Oncology 2020-11-10 2020-08-14 /pmc/articles/PMC7655021/ /pubmed/32795228 http://dx.doi.org/10.1200/JCO.20.01035 Text en © 2020 by American Society of Clinical Oncology https://creativecommons.org/licenses/by-nc-nd/4.0/ Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | RAPID COMMUNICATIONS Abida, Wassim Patnaik, Akash Campbell, David Shapiro, Jeremy Bryce, Alan H. McDermott, Ray Sautois, Brieuc Vogelzang, Nicholas J. Bambury, Richard M. Voog, Eric Zhang, Jingsong Piulats, Josep M. Ryan, Charles J. Merseburger, Axel S. Daugaard, Gedske Heidenreich, Axel Fizazi, Karim Higano, Celestia S. Krieger, Laurence E. Sternberg, Cora N. Watkins, Simon P. Despain, Darrin Simmons, Andrew D. Loehr, Andrea Dowson, Melanie Golsorkhi, Tony Chowdhury, Simon Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration |
title | Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration |
title_full | Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration |
title_fullStr | Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration |
title_full_unstemmed | Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration |
title_short | Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration |
title_sort | rucaparib in men with metastatic castration-resistant prostate cancer harboring a brca1 or brca2 gene alteration |
topic | RAPID COMMUNICATIONS |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655021/ https://www.ncbi.nlm.nih.gov/pubmed/32795228 http://dx.doi.org/10.1200/JCO.20.01035 |
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