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Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID)
Capivasertib is a pan-AKT inhibitor. Preclinical data indicate activity in metastatic castration-resistant prostate cancer (mCRPC) and synergism with docetaxel. PATIENTS AND METHODS: ProCAID was a placebo controlled randomized phase II trial in mCRPC. Patients received up to ten 21-day cycles of doc...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Clinical Oncology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078455/ https://www.ncbi.nlm.nih.gov/pubmed/33326257 http://dx.doi.org/10.1200/JCO.20.01576 |
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author | Crabb, Simon J. Griffiths, Gareth Marwood, Ellice Dunkley, Denise Downs, Nichola Martin, Karen Light, Michelle Northey, Josh Wilding, Sam Whitehead, Amy Shaw, Emily Birtle, Alison J. Bahl, Amit Elliott, Tony Westbury, Charlotte Sundar, Santhanam Robinson, Angus Jagdev, Satinder Kumar, Satish Rooney, Claire Salinas-Souza, Carolina Stephens, Christine Khoo, Vincent Jones, Robert J. |
author_facet | Crabb, Simon J. Griffiths, Gareth Marwood, Ellice Dunkley, Denise Downs, Nichola Martin, Karen Light, Michelle Northey, Josh Wilding, Sam Whitehead, Amy Shaw, Emily Birtle, Alison J. Bahl, Amit Elliott, Tony Westbury, Charlotte Sundar, Santhanam Robinson, Angus Jagdev, Satinder Kumar, Satish Rooney, Claire Salinas-Souza, Carolina Stephens, Christine Khoo, Vincent Jones, Robert J. |
author_sort | Crabb, Simon J. |
collection | PubMed |
description | Capivasertib is a pan-AKT inhibitor. Preclinical data indicate activity in metastatic castration-resistant prostate cancer (mCRPC) and synergism with docetaxel. PATIENTS AND METHODS: ProCAID was a placebo controlled randomized phase II trial in mCRPC. Patients received up to ten 21-day cycles of docetaxel (75 mg/m(2) intravenous, day 1) and prednisolone (5 mg twice daily, oral, day 1-21) and were randomly assigned (1:1) to oral capivasertib (320 mg twice daily, 4 days on/3 days off, from day 2 each cycle), or placebo, until disease progression. Treatment allocation used minimization factors: bone metastases; visceral metastases; investigational site; and prior abiraterone or enzalutamide. The primary objective, by intention to treat, determined if the addition of capivasertib prolonged a composite progression-free survival (cPFS) end point that included prostate-specific antigen progression events. cPFS and overall survival (OS) were also assessed by composite biomarker subgroup for PI3K/AKT/PTEN pathway activation status. RESULTS: One hundred and fifty patients were enrolled. Median cPFS was 7.03 (95% CI, 6.28 to 8.25) and 6.70 months (95% CI, 5.52 to 7.36) with capivasertib and placebo respectively (hazard ratio [HR], 0.92; 80% CI, 0.73 to 1.16; one-sided P = .32). Median OS was 31.15 (95% CI, 20.07 to not reached) and 20.27 months (95% CI, 17.51 to 24.18), respectively (HR, 0.54; 95% CI, 0.34 to 0.88; two-sided P = .01). cPFS and OS results were consistent irrespective of PI3K/AKT/PTEN pathway activation status. Grade III-IV adverse events were equivalent between arms (62.2%). The most common adverse events of any grade deemed related to capivasertib were diarrhea, fatigue, nausea, and rash. CONCLUSION: The addition of capivasertib to chemotherapy did not extend cPFS in mCRPC irrespective of PI3K/AKT/PTEN pathway activation status. The observed OS result (a secondary end point) will require prospective validation in future studies to address potential for bias. |
format | Online Article Text |
id | pubmed-8078455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society of Clinical Oncology |
record_format | MEDLINE/PubMed |
spelling | pubmed-80784552022-01-20 Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID) Crabb, Simon J. Griffiths, Gareth Marwood, Ellice Dunkley, Denise Downs, Nichola Martin, Karen Light, Michelle Northey, Josh Wilding, Sam Whitehead, Amy Shaw, Emily Birtle, Alison J. Bahl, Amit Elliott, Tony Westbury, Charlotte Sundar, Santhanam Robinson, Angus Jagdev, Satinder Kumar, Satish Rooney, Claire Salinas-Souza, Carolina Stephens, Christine Khoo, Vincent Jones, Robert J. J Clin Oncol ORIGINAL REPORTS Capivasertib is a pan-AKT inhibitor. Preclinical data indicate activity in metastatic castration-resistant prostate cancer (mCRPC) and synergism with docetaxel. PATIENTS AND METHODS: ProCAID was a placebo controlled randomized phase II trial in mCRPC. Patients received up to ten 21-day cycles of docetaxel (75 mg/m(2) intravenous, day 1) and prednisolone (5 mg twice daily, oral, day 1-21) and were randomly assigned (1:1) to oral capivasertib (320 mg twice daily, 4 days on/3 days off, from day 2 each cycle), or placebo, until disease progression. Treatment allocation used minimization factors: bone metastases; visceral metastases; investigational site; and prior abiraterone or enzalutamide. The primary objective, by intention to treat, determined if the addition of capivasertib prolonged a composite progression-free survival (cPFS) end point that included prostate-specific antigen progression events. cPFS and overall survival (OS) were also assessed by composite biomarker subgroup for PI3K/AKT/PTEN pathway activation status. RESULTS: One hundred and fifty patients were enrolled. Median cPFS was 7.03 (95% CI, 6.28 to 8.25) and 6.70 months (95% CI, 5.52 to 7.36) with capivasertib and placebo respectively (hazard ratio [HR], 0.92; 80% CI, 0.73 to 1.16; one-sided P = .32). Median OS was 31.15 (95% CI, 20.07 to not reached) and 20.27 months (95% CI, 17.51 to 24.18), respectively (HR, 0.54; 95% CI, 0.34 to 0.88; two-sided P = .01). cPFS and OS results were consistent irrespective of PI3K/AKT/PTEN pathway activation status. Grade III-IV adverse events were equivalent between arms (62.2%). The most common adverse events of any grade deemed related to capivasertib were diarrhea, fatigue, nausea, and rash. CONCLUSION: The addition of capivasertib to chemotherapy did not extend cPFS in mCRPC irrespective of PI3K/AKT/PTEN pathway activation status. The observed OS result (a secondary end point) will require prospective validation in future studies to address potential for bias. American Society of Clinical Oncology 2021-01-20 2020-12-16 /pmc/articles/PMC8078455/ /pubmed/33326257 http://dx.doi.org/10.1200/JCO.20.01576 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 | ORIGINAL REPORTS Crabb, Simon J. Griffiths, Gareth Marwood, Ellice Dunkley, Denise Downs, Nichola Martin, Karen Light, Michelle Northey, Josh Wilding, Sam Whitehead, Amy Shaw, Emily Birtle, Alison J. Bahl, Amit Elliott, Tony Westbury, Charlotte Sundar, Santhanam Robinson, Angus Jagdev, Satinder Kumar, Satish Rooney, Claire Salinas-Souza, Carolina Stephens, Christine Khoo, Vincent Jones, Robert J. Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID) |
title | Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID) |
title_full | Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID) |
title_fullStr | Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID) |
title_full_unstemmed | Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID) |
title_short | Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID) |
title_sort | pan-akt inhibitor capivasertib with docetaxel and prednisolone in metastatic castration-resistant prostate cancer: a randomized, placebo-controlled phase ii trial (procaid) |
topic | ORIGINAL REPORTS |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078455/ https://www.ncbi.nlm.nih.gov/pubmed/33326257 http://dx.doi.org/10.1200/JCO.20.01576 |
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