Revision as of 12:48, 2 January 2023

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.

Metastatic castration-resistant

Olaparib monotherapy

Regimen variant #1, 300 mg BID

FDA-recommended dose

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
de Bono et al. 2020 (PROfound)	2017-2018	Phase 3 (E-RT-ooc)	1. Abiraterone 2. Enzalutamide	Seems to have superior OS¹ 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

Targeted therapy

Olaparib (Lynparza) 300 mg PO twice per day

Continued indefinitely

Regimen variant #2, 400 mg BID

Study	Evidence
Kaufman et al. 2014 (Study 42)	Phase 2, <20 pts in subgroup
Mateo et al. 2015 (TOPARP-A)	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

Targeted therapy

Olaparib (Lynparza) 400 mg PO twice per day

Continued indefinitely

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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript link to supplementary appendix PubMed NCT02987543
1. 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

Rucaparib monotherapy

Regimen

Study	Years of enrollment	Evidence
Awaiting publication (TRITON2)	2017-NR	Phase 2 (RT)

Note: this study is the basis of FDA approval; however, no dosing details are provided on CT.gov and there are no published manuscripts to date.

Targeted therapy

Rucaparib (Rubraca)

References

TRITON2: NCT02952534

@@ Line 10: / Line 10: @@
 |}
 <big>'''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.'''</big>
 {{TOC limit|limit=3}}
 =Metastatic castration-resistant=
 ==Olaparib monotherapy {{#subobject:defe72|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen Variant #1, 300 mg BID {{#subobject:8979a4|Variant=1}}===
+===Regimen variant #1, 300 mg BID {{#subobject:8979a4|Variant=1}}===
 {| class="wikitable sortable" style="color:white; background-color:#404040"
 |<small>'''FDA-recommended dose'''</small>
@@ Line 36: / Line 34: @@
 |}
 ''<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====
 *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
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Olaparib (Lynparza)]] 300 mg PO twice per day
 '''Continued indefinitely'''
+</div></div><br>
-===Regimen Variant #2, 400 mg BID {{#subobject:8979a3|Variant=1}}===
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 400 mg BID {{#subobject:8979a3|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
 ! style="width: 25%" |Study
@@ Line 61: / Line 59: @@
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
 ====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
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Olaparib (Lynparza)]] 400 mg PO twice per day
 '''Continued indefinitely'''
+</div></div>
 ===References===
 <!-- 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] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6057749/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25366685 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. [https://doi.org/10.1056/NEJMoa1506859 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5228595/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26510020 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. [http://doi.org/10.1056/NEJMoa1911440 link to original article] '''contains dosing details in manuscript''' [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] 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]
 ==Rucaparib monotherapy {{#subobject:72fd0c|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:68aa39|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 93: / Line 89: @@
 |}
 ''Note: this study is the basis of FDA approval; however, no dosing details are provided on CT.gov and there are no published manuscripts to date.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Rucaparib (Rubraca)]]
+</div></div>
 ===References===
 # '''TRITON2:''' NCT02952534
 [[Category:Prostate cancer regimens]]
 [[Category:Biomarker-specific pages]]
 [[Category:Genitourinary cancers]]

Difference between revisions of "Prostate cancer, BRCA-mutated"

Revision as of 12:48, 2 January 2023

Contents

Metastatic castration-resistant

Olaparib monotherapy

Regimen variant #1, 300 mg BID

Prior treatment criteria

Biomarker eligibility criteria

Targeted therapy

Regimen variant #2, 400 mg BID

Biomarker eligibility criteria

Targeted therapy

References

Rucaparib monotherapy

Regimen

Targeted therapy

References

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