Difference between revisions of "Prostate cancer, BRCA-mutated"
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div> | <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div> | ||
|} | |} | ||
− | + | '''Note: this page has regimens which are specific to prostate cancer that is BRCA-mutated. Please see the [[Prostate cancer|main prostate cancer]] page for other regimens.''' | |
− | |||
{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
+ | =Guidelines= | ||
+ | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' | ||
+ | ==NCCN== | ||
+ | *''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459 NCCN Guidelines - Prostate Cancer].'' | ||
=Metastatic castration-resistant= | =Metastatic castration-resistant= | ||
+ | ==Abiraterone monotherapy {{#subobject:deikoc|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:oq0b24|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates of enrollment | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064172/ Fizazi et al. 2023 (TRITON3)] | ||
+ | |2017-02-08 to 2022-02-02 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Rucaparib_monotherapy|Rucaparib]] | ||
+ | | style="background-color:#d73027" |Inferior PFSi (primary endpoint) | ||
+ | |- | ||
+ | |[http://doi.org/10.1056/NEJMoa1911440 de Bono et al. 2020 (PROfound)] | ||
+ | |2017-04 to 2018-11 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Olaparib_monotherapy|Olaparib]] | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10431499/ Chi et al. 2023 (MAGNITUDE)] | ||
+ | |2019-05 to 2021-03 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Abiraterone_.26_Niraparib|Abiraterone & Niraparib]] | ||
+ | | style="background-color:#d73027" |Inferior rPFS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Endocrine therapy==== | ||
+ | *[[Abiraterone (Zytiga)]] 1000 mg PO once per day on days 1 to 28 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Prednisone (Sterapred)]] 5 mg PO twice per day or 10 mg PO once per day on days 1 to 28 | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''PROfound:''' de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. Epub 2020 Apr 28. [http://doi.org/10.1056/NEJMoa1911440 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1911440/suppl_file/nejmoa1911440_appendix.pdf link to supplementary appendix] [https://pubmed.ncbi.nlm.nih.gov/32343890/ PubMed] [https://clinicaltrials.gov/study/NCT02987543 NCT02987543] | ||
+ | ## '''Update:''' Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Özgüroğlu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Dec 10;383(24):2345-2357. Epub 2020 Sep 20. [https://doi.org/10.1056/nejmoa2022485 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32955174/ PubMed] | ||
+ | ## '''HRQoL analysis:''' Thiery-Vuillemin A, de Bono J, Hussain M, Roubaud G, Procopio G, Shore N, Fizazi K, Dos Anjos G, Gravis G, Joung JY, Matsubara N, Castellano D, Degboe A, Gresty C, Kang J, Allen A, Poehlein C, Saad F. Pain and health-related quality of life with olaparib versus physician's choice of next-generation hormonal drug in patients with metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations (PROfound): an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Mar;23(3):393-405. Epub 2022 Feb 11. Erratum in: Lancet Oncol. 2022 Apr;23(4):e161. [https://doi.org/10.1016/S1470-2045(22)00017-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35157830/ PubMed] | ||
+ | #'''TRITON3:''' Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. Epub 2023 Feb 16. [https://doi.org/10.1056/NEJMoa2214676 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064172/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36795891/ PubMed] [https://clinicaltrials.gov/study/NCT02975934 NCT02975934] | ||
+ | #'''MAGNITUDE:''' Chi KN, Rathkopf D, Smith MR, Efstathiou E, Attard G, Olmos D, Lee JY, Small EJ, Pereira de Santana Gomes AJ, Roubaud G, Saad M, Zurawski B, Sakalo V, Mason GE, Francis P, Wang G, Wu D, Diorio B, Lopez-Gitlitz A, Sandhu S; MAGNITUDE Principal Investigators. Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2023 Jun 20;41(18):3339-3351. Epub 2023 Mar 23. [https://doi.org/10.1200/jco.22.01649 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10431499/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36952634/ PubMed] [https://clinicaltrials.gov/study/NCT03748641 NCT03748641] | ||
+ | ##'''Update:''' Chi KN, Sandhu S, Smith MR, Attard G, Saad M, Olmos D, Castro E, Roubaud G, Pereira de Santana Gomes AJ, Small EJ, Rathkopf DE, Gurney H, Jung W, Mason GE, Dibaj S, Wu D, Diorio B, Urtishak K, Del Corral A, Francis P, Kim W, Efstathiou E. Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial. Ann Oncol. 2023 Sep;34(9):772-782. Epub 2023 Jul 1. [https://doi.org/10.1016/j.annonc.2023.06.009 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10849465/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37399894/ PubMed] | ||
+ | |||
+ | ==Abiraterone & Niraparib {{#subobject:dei9gc|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:8jvu24|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates of enrollment | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10431499/ Chi et al. 2023 (MAGNITUDE)] | ||
+ | |2019-05 to 2021-03 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
+ | |[[#Abiraterone_monotherapy|Abiraterone]] | ||
+ | | style="background-color:#1a9850" |Superior rPFS (primary endpoint)<br>Median rPFS: 16.6 vs 10.9 mo<br>(HR 0.53, 95% CI 0.36-0.79) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Anticancer therapy==== | ||
+ | *[[Niraparib and abiraterone (Akeega)]] 200/1000 mg PO once per day | ||
+ | ====Supportive therapy==== | ||
+ | *[[Prednisone (Sterapred)]] 5 mg PO twice per day | ||
+ | '''Continued indefinitely''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''MAGNITUDE:''' Chi KN, Rathkopf D, Smith MR, Efstathiou E, Attard G, Olmos D, Lee JY, Small EJ, Pereira de Santana Gomes AJ, Roubaud G, Saad M, Zurawski B, Sakalo V, Mason GE, Francis P, Wang G, Wu D, Diorio B, Lopez-Gitlitz A, Sandhu S; MAGNITUDE Principal Investigators. Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2023 Jun 20;41(18):3339-3351. Epub 2023 Mar 23. [https://doi.org/10.1200/jco.22.01649 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10431499/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36952634/ PubMed] [https://clinicaltrials.gov/study/NCT03748641 NCT03748641] | ||
+ | ##'''Update:''' Chi KN, Sandhu S, Smith MR, Attard G, Saad M, Olmos D, Castro E, Roubaud G, Pereira de Santana Gomes AJ, Small EJ, Rathkopf DE, Gurney H, Jung W, Mason GE, Dibaj S, Wu D, Diorio B, Urtishak K, Del Corral A, Francis P, Kim W, Efstathiou E. Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial. Ann Oncol. 2023 Sep;34(9):772-782. Epub 2023 Jul 1. [https://doi.org/10.1016/j.annonc.2023.06.009 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10849465/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37399894/ PubMed] | ||
+ | |||
+ | ==Docetaxel & Prednisone {{#subobject:8yq3z3 |Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:1c3c28 |Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates of enrollment | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064172/ Fizazi et al. 2023 (TRITON3)] | ||
+ | |2017-02-08 to 2022-02-02 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Rucaparib_monotherapy|Rucaparib]] | ||
+ | | style="background-color:#d73027" |Inferior PFSi (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Endocrine therapy==== | ||
+ | *[[Prednisone (Sterapred)]] 5 mg PO twice per day on days 1 to 21 | ||
+ | '''21-day cycle for up to 10 cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''TRITON3:''' Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. Epub 2023 Feb 16. [https://doi.org/10.1056/NEJMoa2214676 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064172/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36795891/ PubMed] [https://clinicaltrials.gov/study/NCT02975934 NCT02975934] | ||
+ | ==Docetaxel & Prednisolone {{#subobject:8jfyz3 |Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:agck28 |Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates of enrollment | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064172/ Fizazi et al. 2023 (TRITON3)] | ||
+ | |2017-02-08 to 2022-02-02 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Rucaparib_monotherapy|Rucaparib]] | ||
+ | | style="background-color:#d73027" |Inferior PFSi (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Endocrine therapy==== | ||
+ | *[[Prednisolone (Millipred)]] 5 mg PO twice per day on days 1 to 21 | ||
+ | '''21-day cycle for up to 10 cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''TRITON3:''' Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. Epub 2023 Feb 16. [https://doi.org/10.1056/NEJMoa2214676 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064172/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36795891/ PubMed] [https://clinicaltrials.gov/study/NCT02975934 NCT02975934] | ||
+ | ==Enzalutamide monotherapy {{#subobject:9jgkoc|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:ckb224|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates of enrollment | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064172/ Fizazi et al. 2023 (TRITON3)] | ||
+ | |2017-02-08 to 2022-02-02 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Rucaparib_monotherapy|Rucaparib]] | ||
+ | | style="background-color:#d73027" |Inferior PFSi (primary endpoint) | ||
+ | |- | ||
+ | |[http://doi.org/10.1056/NEJMoa1911440 de Bono et al. 2020 (PROfound)] | ||
+ | |2017-04 to 2018-11 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Olaparib_monotherapy|Olaparib]] | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Endocrine therapy==== | ||
+ | *[[Enzalutamide (Xtandi)]] 160 mg PO once per day | ||
+ | '''Continued indefinitely''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''PROfound:''' de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. Epub 2020 Apr 28. [http://doi.org/10.1056/NEJMoa1911440 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1911440/suppl_file/nejmoa1911440_appendix.pdf link to supplementary appendix] [https://pubmed.ncbi.nlm.nih.gov/32343890/ PubMed] [https://clinicaltrials.gov/study/NCT02987543 NCT02987543] | ||
+ | ## '''Update:''' Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Özgüroğlu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Dec 10;383(24):2345-2357. Epub 2020 Sep 20. [https://doi.org/10.1056/nejmoa2022485 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32955174/ PubMed] | ||
+ | ## '''HRQoL analysis:''' Thiery-Vuillemin A, de Bono J, Hussain M, Roubaud G, Procopio G, Shore N, Fizazi K, Dos Anjos G, Gravis G, Joung JY, Matsubara N, Castellano D, Degboe A, Gresty C, Kang J, Allen A, Poehlein C, Saad F. Pain and health-related quality of life with olaparib versus physician's choice of next-generation hormonal drug in patients with metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations (PROfound): an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Mar;23(3):393-405. Epub 2022 Feb 11. Erratum in: Lancet Oncol. 2022 Apr;23(4):e161. [https://doi.org/10.1016/S1470-2045(22)00017-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35157830/ PubMed] | ||
+ | #'''TRITON3:''' Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. Epub 2023 Feb 16. [https://doi.org/10.1056/NEJMoa2214676 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064172/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36795891/ PubMed] [https://clinicaltrials.gov/study/NCT02975934 NCT02975934] | ||
+ | |||
==Olaparib monotherapy {{#subobject:defe72|Regimen=1}}== | ==Olaparib monotherapy {{#subobject:defe72|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen | + | ===Regimen variant #1, 300 mg twice per day {{#subobject:8979a4|Variant=1}}=== |
{| class="wikitable sortable" style="color:white; background-color:#404040" | {| class="wikitable sortable" style="color:white; background-color:#404040" | ||
|<small>'''FDA-recommended dose'''</small> | |<small>'''FDA-recommended dose'''</small> | ||
Line 32: | Line 184: | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
− | |||
− | |||
− | |||
|- | |- | ||
|[http://doi.org/10.1056/NEJMoa1911440 de Bono et al. 2020 (PROfound)] | |[http://doi.org/10.1056/NEJMoa1911440 de Bono et al. 2020 (PROfound)] | ||
− | |2017-2018 | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | | style="background-color:#1a9851" |Phase 3 (E-RT-ooc) | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-216-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' |
− | | | + | |- |
− | | style="background-color:# | + | |} --> |
− | + | |2017-04 to 2018-11 | |
− | + | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc) | |
− | + | |Physician's choice of:<br>1a. [[#Abiraterone_monotherapy|Abiraterone]]<br>1b. [[#Enzalutamide_monotherapy|Enzalutamide]] | |
+ | | style="background-color:#91cf60" |Superior rPFS (primary endpoint)<br>Median rPFS: 7.4 vs 3.6 mo<br>(HR 0.34, 95% CI 0.25-0.47)<br><br>Seems to have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 19.1 vs 14.7 mo<br>(HR 0.69, 95% CI 0.50-0.97) | ||
|- | |- | ||
|} | |} | ||
− | ''<sup>1</sup> | + | ''<sup>1</sup>Reported efficacy is for patients in Cohort A in the 2020 update.'' |
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *Progression on abiraterone or enzalutamide | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
− | |||
*Cohort A: 1+ alterations in BRCA1, BRCA2, or ATM | *Cohort A: 1+ alterations in BRCA1, BRCA2, or ATM | ||
*Cohort B: 1+ alterations in BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L | *Cohort B: 1+ alterations in BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Olaparib (Lynparza)]] 300 mg PO twice per day | *[[Olaparib (Lynparza)]] 300 mg PO twice per day | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div><br> | |
− | ===Regimen | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #2, 400 mg twice per day {{#subobject:8979a3|Variant=1}}=== |
− | ! style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6057749/ Kaufman et al. 2014 (Study 42)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6057749/ Kaufman et al. 2014 (Study 42)] | ||
− | | style="background-color:#ffffbe" |Phase 2, | + | |2010-02-21 to 2012-07-31 |
+ | | style="background-color:#ffffbe" |Phase 2, fewer than 20 pts in subgroup | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5228595/ Mateo et al. 2015 (TOPARP-A)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5228595/ Mateo et al. 2015 (TOPARP-A)] | ||
+ | |2012-07 to 2014-09 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*Study 42: Germline BRCA1/2 mutations and had progression on hormonal and one systemic therapy | *Study 42: Germline BRCA1/2 mutations and had progression on hormonal and one systemic therapy | ||
*TOPARP-A: Patients who were found to have homozygous deletions, deleterious mutations, or both in DNA-repair genes were much more likely to respond to olaparib | *TOPARP-A: Patients who were found to have homozygous deletions, deleterious mutations, or both in DNA-repair genes were much more likely to respond to olaparib | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Olaparib (Lynparza)]] 400 mg PO twice per day | *[[Olaparib (Lynparza)]] 400 mg PO twice per day | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- Presented at the 49th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 4, 2013. --> | <!-- Presented at the 49th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 4, 2013. --> | ||
− | + | #'''Study 42:''' Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. [https://doi.org/10.1200/jco.2014.56.2728 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6057749/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25366685/ PubMed] [https://clinicaltrials.gov/study/NCT01078662 NCT01078662] | |
− | #'''Study 42:''' Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. [https://doi.org/10.1200/jco.2014.56.2728 link to original article] ''' | + | #'''TOPARP-A:''' Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, Nava Rodrigues D, Robinson D, Omlin A, Tunariu N, Boysen G, Porta N, Flohr P, Gillman A, Figueiredo I, Paulding C, Seed G, Jain S, Ralph C, Protheroe A, Hussain S, Jones R, Elliott T, McGovern U, Bianchini D, Goodall J, Zafeiriou Z, Williamson CT, Ferraldeschi R, Riisnaes R, Ebbs B, Fowler G, Roda D, Yuan W, Wu YM, Cao X, Brough R, Pemberton H, A'Hern R, Swain A, Kunju LP, Eeles R, Attard G, Lord CJ, Ashworth A, Rubin MA, Knudsen KE, Feng FY, Chinnaiyan AM, Hall E, de Bono JS. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med. 2015 Oct 29;373(18):1697-708. [https://doi.org/10.1056/NEJMoa1506859 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5228595/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26510020/ PubMed] [https://clinicaltrials.gov/study/NCT01682772 NCT01682772] |
− | #'''TOPARP-A:''' Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, Nava Rodrigues D, Robinson D, Omlin A, Tunariu N, Boysen G, Porta N, Flohr P, Gillman A, Figueiredo I, Paulding C, Seed G, Jain S, Ralph C, Protheroe A, Hussain S, Jones R, Elliott T, McGovern U, Bianchini D, Goodall J, Zafeiriou Z, Williamson CT, Ferraldeschi R, Riisnaes R, Ebbs B, Fowler G, Roda D, Yuan W, Wu YM, Cao X, Brough R, Pemberton H, A'Hern R, Swain A, Kunju LP, Eeles R, Attard G, Lord CJ, Ashworth A, Rubin MA, Knudsen KE, Feng FY, Chinnaiyan AM, Hall E, de Bono JS. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med. 2015 Oct 29;373(18):1697-708. [https:// | + | #'''PROfound:''' de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. Epub 2020 Apr 28. [http://doi.org/10.1056/NEJMoa1911440 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1911440/suppl_file/nejmoa1911440_appendix.pdf link to supplementary appendix] [https://pubmed.ncbi.nlm.nih.gov/32343890/ PubMed] [https://clinicaltrials.gov/study/NCT02987543 NCT02987543] |
− | #'''PROfound:''' de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. Epub 2020 Apr 28. [http://doi.org/10.1056/NEJMoa1911440 link to original article] ''' | + | ## '''Update:''' Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Özgüroğlu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Dec 10;383(24):2345-2357. Epub 2020 Sep 20. [https://doi.org/10.1056/nejmoa2022485 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32955174/ PubMed] |
− | ## '''Update:''' Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Özgüroğlu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Dec 10;383(24):2345-2357. Epub 2020 Sep 20. [https://doi.org/10.1056/nejmoa2022485 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32955174 PubMed] | + | ## '''HRQoL analysis:''' Thiery-Vuillemin A, de Bono J, Hussain M, Roubaud G, Procopio G, Shore N, Fizazi K, Dos Anjos G, Gravis G, Joung JY, Matsubara N, Castellano D, Degboe A, Gresty C, Kang J, Allen A, Poehlein C, Saad F. Pain and health-related quality of life with olaparib versus physician's choice of next-generation hormonal drug in patients with metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations (PROfound): an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Mar;23(3):393-405. Epub 2022 Feb 11. Erratum in: Lancet Oncol. 2022 Apr;23(4):e161. [https://doi.org/10.1016/S1470-2045(22)00017-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35157830/ PubMed] |
==Rucaparib monotherapy {{#subobject:72fd0c|Regimen=1}}== | ==Rucaparib monotherapy {{#subobject:72fd0c|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:68aa39|Variant=1}}=== | ===Regimen {{#subobject:68aa39|Variant=1}}=== | ||
− | {| class="wikitable sortable" style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | ! style="width: 20%" |Study |
− | !style="width: | + | ! style="width: 20%" |Dates of enrollment |
− | !style="width: | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7655021/ Abida et al. 2020 (TRITON2)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-230-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
|- | |- | ||
− | | | + | |} --> |
− | |2017 | + | |2017 to not reported |
|style="background-color:#91cf61"|Phase 2 (RT) | |style="background-color:#91cf61"|Phase 2 (RT) | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064172/ Fizazi et al. 2023 (TRITON3)] | ||
+ | |2017-02-08 to 2022-02-02 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
+ | |Physician's choice of:<br>1a. [[#Abiraterone_monotherapy|Abiraterone]]<br>1b. [[#Enzalutamide_monotherapy|Enzalutamide]]<br>1c. [[#Docetaxel_.26_Prednisone|Docetaxel & Prednisone]]<br>1d. [[#Docetaxel_.26_Prednisolone|Docetaxel & Prednisolone]] | ||
+ | | style="background-color:#1a9850" |Superior PFSi (primary endpoint)<br>Median PFSi: 10.2 vs 6.4 mo<br>(HR 0.61, 95% CI 0.47-0.80) | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
+ | ====Prior treatment criteria==== | ||
+ | *TRITON3: Progression after treatment with a second-generation androgen-receptor pathway inhibitor | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *TRITON3: 1+ alterations in BRCA1, BRCA2, or ATM | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Rucaparib (Rubraca)]] | + | *[[Rucaparib (Rubraca)]] 600 mg PO twice per day on days 1 to 28 |
− | + | '''28-day cycles''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''TRITON2:''' NCT02952534 | + | # '''TRITON2:''' Abida W, Patnaik A, Campbell D, Shapiro J, Bryce AH, McDermott R, Sautois B, Vogelzang NJ, Bambury RM, Voog E, Zhang J, Piulats JM, Ryan CJ, Merseburger AS, Daugaard G, Heidenreich A, Fizazi K, Higano CS, Krieger LE, Sternberg CN, Watkins SP, Despain D, Simmons AD, Loehr A, Dowson M, Golsorkhi T, Chowdhury S; TRITON2 investigators. Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration. J Clin Oncol. 2020 Nov 10;38(32):3763-3772. Epub 2020 Aug 14. [https://doi.org/10.1200/jco.20.01035 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7655021/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32795228/ PubMed] [https://clinicaltrials.gov/study/NCT02952534 NCT02952534] |
− | + | #'''TRITON3:''' Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. Epub 2023 Feb 16. [https://doi.org/10.1056/NEJMoa2214676 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064172/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36795891/ PubMed] [https://clinicaltrials.gov/study/NCT02975934 NCT02975934] | |
[[Category:Prostate cancer regimens]] | [[Category:Prostate cancer regimens]] | ||
[[Category:Biomarker-specific pages]] | [[Category:Biomarker-specific pages]] | ||
− | [[Category: | + | [[Category:Male genital cancers]] |
Latest revision as of 17:13, 17 July 2024
Page editor | Section editor | ||
---|---|---|---|
Laura S. Graham, MD University of Colorado Anschutz Medical Campus Aurora, CO, USA |
Ali Raza Khaki, MD Stanford University Palo Alto, CA, USA |
7 regimens on this page
8 variants on this page
|
Note: this page has regimens which are specific to prostate cancer that is BRCA-mutated. Please see the main prostate cancer page for other regimens.
Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Prostate Cancer.
Metastatic castration-resistant
Abiraterone monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fizazi et al. 2023 (TRITON3) | 2017-02-08 to 2022-02-02 | Phase 3 (C) | Rucaparib | Inferior PFSi (primary endpoint) |
de Bono et al. 2020 (PROfound) | 2017-04 to 2018-11 | Phase 3 (C) | Olaparib | Seems to have inferior OS |
Chi et al. 2023 (MAGNITUDE) | 2019-05 to 2021-03 | Phase 3 (C) | Abiraterone & Niraparib | Inferior rPFS |
Endocrine therapy
- Abiraterone (Zytiga) 1000 mg PO once per day on days 1 to 28
Supportive therapy
- Prednisone (Sterapred) 5 mg PO twice per day or 10 mg PO once per day on days 1 to 28
28-day cycles
References
- PROfound: de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. Epub 2020 Apr 28. link to original article dosing details in manuscript have been reviewed by our editors link to supplementary appendix PubMed NCT02987543
- Update: Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Özgüroğlu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Dec 10;383(24):2345-2357. Epub 2020 Sep 20. link to original article PubMed
- HRQoL analysis: Thiery-Vuillemin A, de Bono J, Hussain M, Roubaud G, Procopio G, Shore N, Fizazi K, Dos Anjos G, Gravis G, Joung JY, Matsubara N, Castellano D, Degboe A, Gresty C, Kang J, Allen A, Poehlein C, Saad F. Pain and health-related quality of life with olaparib versus physician's choice of next-generation hormonal drug in patients with metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations (PROfound): an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Mar;23(3):393-405. Epub 2022 Feb 11. Erratum in: Lancet Oncol. 2022 Apr;23(4):e161. link to original article PubMed
- TRITON3: Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. Epub 2023 Feb 16. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed NCT02975934
- MAGNITUDE: Chi KN, Rathkopf D, Smith MR, Efstathiou E, Attard G, Olmos D, Lee JY, Small EJ, Pereira de Santana Gomes AJ, Roubaud G, Saad M, Zurawski B, Sakalo V, Mason GE, Francis P, Wang G, Wu D, Diorio B, Lopez-Gitlitz A, Sandhu S; MAGNITUDE Principal Investigators. Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2023 Jun 20;41(18):3339-3351. Epub 2023 Mar 23. link to original article link to PMC article PubMed NCT03748641
- Update: Chi KN, Sandhu S, Smith MR, Attard G, Saad M, Olmos D, Castro E, Roubaud G, Pereira de Santana Gomes AJ, Small EJ, Rathkopf DE, Gurney H, Jung W, Mason GE, Dibaj S, Wu D, Diorio B, Urtishak K, Del Corral A, Francis P, Kim W, Efstathiou E. Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial. Ann Oncol. 2023 Sep;34(9):772-782. Epub 2023 Jul 1. link to original article link to PMC article PubMed
Abiraterone & Niraparib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Chi et al. 2023 (MAGNITUDE) | 2019-05 to 2021-03 | Phase 3 (E-RT-esc) | Abiraterone | Superior rPFS (primary endpoint) Median rPFS: 16.6 vs 10.9 mo (HR 0.53, 95% CI 0.36-0.79) |
Anticancer therapy
- Niraparib and abiraterone (Akeega) 200/1000 mg PO once per day
Supportive therapy
- Prednisone (Sterapred) 5 mg PO twice per day
Continued indefinitely
References
- MAGNITUDE: Chi KN, Rathkopf D, Smith MR, Efstathiou E, Attard G, Olmos D, Lee JY, Small EJ, Pereira de Santana Gomes AJ, Roubaud G, Saad M, Zurawski B, Sakalo V, Mason GE, Francis P, Wang G, Wu D, Diorio B, Lopez-Gitlitz A, Sandhu S; MAGNITUDE Principal Investigators. Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2023 Jun 20;41(18):3339-3351. Epub 2023 Mar 23. link to original article link to PMC article PubMed NCT03748641
- Update: Chi KN, Sandhu S, Smith MR, Attard G, Saad M, Olmos D, Castro E, Roubaud G, Pereira de Santana Gomes AJ, Small EJ, Rathkopf DE, Gurney H, Jung W, Mason GE, Dibaj S, Wu D, Diorio B, Urtishak K, Del Corral A, Francis P, Kim W, Efstathiou E. Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial. Ann Oncol. 2023 Sep;34(9):772-782. Epub 2023 Jul 1. link to original article link to PMC article PubMed
Docetaxel & Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fizazi et al. 2023 (TRITON3) | 2017-02-08 to 2022-02-02 | Phase 3 (C) | Rucaparib | Inferior PFSi (primary endpoint) |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Endocrine therapy
- Prednisone (Sterapred) 5 mg PO twice per day on days 1 to 21
21-day cycle for up to 10 cycles
References
- TRITON3: Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. Epub 2023 Feb 16. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed NCT02975934
Docetaxel & Prednisolone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fizazi et al. 2023 (TRITON3) | 2017-02-08 to 2022-02-02 | Phase 3 (C) | Rucaparib | Inferior PFSi (primary endpoint) |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Endocrine therapy
- Prednisolone (Millipred) 5 mg PO twice per day on days 1 to 21
21-day cycle for up to 10 cycles
References
- TRITON3: Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. Epub 2023 Feb 16. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed NCT02975934
Enzalutamide monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fizazi et al. 2023 (TRITON3) | 2017-02-08 to 2022-02-02 | Phase 3 (C) | Rucaparib | Inferior PFSi (primary endpoint) |
de Bono et al. 2020 (PROfound) | 2017-04 to 2018-11 | Phase 3 (C) | Olaparib | Seems to have inferior OS |
References
- PROfound: de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. Epub 2020 Apr 28. link to original article dosing details in manuscript have been reviewed by our editors link to supplementary appendix PubMed NCT02987543
- Update: Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Özgüroğlu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Dec 10;383(24):2345-2357. Epub 2020 Sep 20. link to original article PubMed
- HRQoL analysis: Thiery-Vuillemin A, de Bono J, Hussain M, Roubaud G, Procopio G, Shore N, Fizazi K, Dos Anjos G, Gravis G, Joung JY, Matsubara N, Castellano D, Degboe A, Gresty C, Kang J, Allen A, Poehlein C, Saad F. Pain and health-related quality of life with olaparib versus physician's choice of next-generation hormonal drug in patients with metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations (PROfound): an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Mar;23(3):393-405. Epub 2022 Feb 11. Erratum in: Lancet Oncol. 2022 Apr;23(4):e161. link to original article PubMed
- TRITON3: Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. Epub 2023 Feb 16. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed NCT02975934
Olaparib monotherapy
Regimen variant #1, 300 mg twice per day
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
de Bono et al. 2020 (PROfound) | 2017-04 to 2018-11 | Phase 3 (E-RT-switch-ooc) | Physician's choice of: 1a. Abiraterone 1b. Enzalutamide |
Superior rPFS (primary endpoint) Median rPFS: 7.4 vs 3.6 mo (HR 0.34, 95% CI 0.25-0.47) Seems to have superior OS1 (secondary endpoint) Median OS: 19.1 vs 14.7 mo (HR 0.69, 95% CI 0.50-0.97) |
1Reported efficacy is for patients in Cohort A in the 2020 update.
Prior treatment criteria
- Progression on abiraterone or enzalutamide
Biomarker eligibility criteria
- Cohort A: 1+ alterations in BRCA1, BRCA2, or ATM
- Cohort B: 1+ alterations in BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L
Regimen variant #2, 400 mg twice per day
Study | Dates of enrollment | Evidence |
---|---|---|
Kaufman et al. 2014 (Study 42) | 2010-02-21 to 2012-07-31 | Phase 2, fewer than 20 pts in subgroup |
Mateo et al. 2015 (TOPARP-A) | 2012-07 to 2014-09 | Phase 2 |
Biomarker eligibility criteria
- Study 42: Germline BRCA1/2 mutations and had progression on hormonal and one systemic therapy
- TOPARP-A: Patients who were found to have homozygous deletions, deleterious mutations, or both in DNA-repair genes were much more likely to respond to olaparib
References
- Study 42: Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01078662
- TOPARP-A: Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, Nava Rodrigues D, Robinson D, Omlin A, Tunariu N, Boysen G, Porta N, Flohr P, Gillman A, Figueiredo I, Paulding C, Seed G, Jain S, Ralph C, Protheroe A, Hussain S, Jones R, Elliott T, McGovern U, Bianchini D, Goodall J, Zafeiriou Z, Williamson CT, Ferraldeschi R, Riisnaes R, Ebbs B, Fowler G, Roda D, Yuan W, Wu YM, Cao X, Brough R, Pemberton H, A'Hern R, Swain A, Kunju LP, Eeles R, Attard G, Lord CJ, Ashworth A, Rubin MA, Knudsen KE, Feng FY, Chinnaiyan AM, Hall E, de Bono JS. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med. 2015 Oct 29;373(18):1697-708. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01682772
- PROfound: de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. Epub 2020 Apr 28. link to original article dosing details in manuscript have been reviewed by our editors link to supplementary appendix PubMed NCT02987543
- Update: Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Özgüroğlu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Dec 10;383(24):2345-2357. Epub 2020 Sep 20. link to original article PubMed
- HRQoL analysis: Thiery-Vuillemin A, de Bono J, Hussain M, Roubaud G, Procopio G, Shore N, Fizazi K, Dos Anjos G, Gravis G, Joung JY, Matsubara N, Castellano D, Degboe A, Gresty C, Kang J, Allen A, Poehlein C, Saad F. Pain and health-related quality of life with olaparib versus physician's choice of next-generation hormonal drug in patients with metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations (PROfound): an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Mar;23(3):393-405. Epub 2022 Feb 11. Erratum in: Lancet Oncol. 2022 Apr;23(4):e161. link to original article PubMed
Rucaparib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Abida et al. 2020 (TRITON2) | 2017 to not reported | Phase 2 (RT) | ||
Fizazi et al. 2023 (TRITON3) | 2017-02-08 to 2022-02-02 | Phase 3 (E-switch-ooc) | Physician's choice of: 1a. Abiraterone 1b. Enzalutamide 1c. Docetaxel & Prednisone 1d. Docetaxel & Prednisolone |
Superior PFSi (primary endpoint) Median PFSi: 10.2 vs 6.4 mo (HR 0.61, 95% CI 0.47-0.80) |
Prior treatment criteria
- TRITON3: Progression after treatment with a second-generation androgen-receptor pathway inhibitor
Biomarker eligibility criteria
- TRITON3: 1+ alterations in BRCA1, BRCA2, or ATM
References
- TRITON2: Abida W, Patnaik A, Campbell D, Shapiro J, Bryce AH, McDermott R, Sautois B, Vogelzang NJ, Bambury RM, Voog E, Zhang J, Piulats JM, Ryan CJ, Merseburger AS, Daugaard G, Heidenreich A, Fizazi K, Higano CS, Krieger LE, Sternberg CN, Watkins SP, Despain D, Simmons AD, Loehr A, Dowson M, Golsorkhi T, Chowdhury S; TRITON2 investigators. Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration. J Clin Oncol. 2020 Nov 10;38(32):3763-3772. Epub 2020 Aug 14. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT02952534
- TRITON3: Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. Epub 2023 Feb 16. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02975934