Difference between revisions of "Ovarian cancer, HRD-positive"

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[[#top|Back to Top]]
 
[[#top|Back to Top]]
 
</div>
 
</div>
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{{#lst:Editorial board transclusions|gyn}}
 
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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>
 
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<big>'''Note: this page has regimens which are specific to ovarian cancer that is BRCA-mutated. Please see the [[Ovarian cancer|main ovarian cancer]] page for other chemotherapy regimens.'''</big>
+
<big>'''Note: this page has regimens which are specific to ovarian cancer with homologous recombination deficiency (HRD). Please see the [[Ovarian cancer|main ovarian cancer]] page for other chemotherapy regimens.'''</big>
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
 
=Guidelines=
 
=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.'''
 
==[http://www.asco.org/ ASCO]==
 
==[http://www.asco.org/ ASCO]==
−
*'''2020:''' Tew et al. [https://doi.org/10.1200/jco.20.01924 PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline]
+
*'''2022:''' Tew et al. [https://doi.org/10.1200/jco.22.01934 Poly(ADP-Ribose) Polymerase Inhibitors in the Management of Ovarian Cancer: ASCO Guideline Rapid Recommendation Update] [https://pubmed.ncbi.nlm.nih.gov/36150092/ PubMed]
 +
**'''2020:''' Tew et al. [https://doi.org/10.1200/jco.20.01924 PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline] [https://www.ncbi.nlm.nih.gov/pubmed/32790492 PubMed]
 +
 
 +
==NCCN==
 +
*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1453 NCCN Guidelines - Ovarian Cancer, Including Fallopian Tube Cancer and Primary Peritoneal Cancer].''
 +
 
 
=Maintenance after first-line therapy=
 
=Maintenance after first-line therapy=
 +
==Bevacizumab monotherapy {{#subobject:1d2514|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:a87d26|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://doi.org/10.1056/nejmoa1911361 Ray-Coquard et al. 2019 (PAOLA-1)]
 +
|2015-2017
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Olaparib_.26_Bevacizumab|Olaparib & Bevacizumab]]
 +
| style="background-color:#d73027" |Inferior PFS
 +
|-
 +
|}
 +
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. The FDA-recommended duration of treatment is 22 cycles (including the 6 cycles of combination chemotherapy).''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*Not specified, but presumably platinum doublet & bevacizumab x 6
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 +
'''21-day cycle for up to 16 cycles'''
 +
</div></div>
 +
===References===
 +
# '''PAOLA-1:''' Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, Fujiwara K, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alía EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marmé F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2416-2428. [https://doi.org/10.1056/nejmoa1911361 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31851799/ PubMed] [https://clinicaltrials.gov/study/NCT02477644 NCT02477644]
 +
##'''Update:''' Ray-Coquard I, Leary A, Pignata S, Cropet C, González-Martín A, Marth C, Nagao S, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alia EM, Bogner G, Yoshida H, Lefeuvre-Plesse C, Buderath P, Mosconi AM, Lortholary A, Burges A, Medioni J, El-Balat A, Rodrigues M, Park-Simon TW, Dubot C, Denschlag D, You B, Pujade-Lauraine E, Harter P; PAOLA-1/ENGOT-ov25 investigators. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ann Oncol. 2023 Aug;34(8):681-692. Epub 2023 May 19. [https://doi.org/10.1016/j.annonc.2023.05.005 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37211045/ PubMed]
 +
 
==Olaparib monotherapy {{#subobject:fac248|Regimen=1}}==
 
==Olaparib monotherapy {{#subobject:fac248|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
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|-
 
|-
 
|[https://doi.org/10.1056/NEJMoa1810858 Moore et al. 2018 (SOLO1)]
 
|[https://doi.org/10.1056/NEJMoa1810858 Moore et al. 2018 (SOLO1)]
−
{| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
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<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
 
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-144-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
 
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-144-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
 
|-
 
|-
−
|}
+
|} -->
 
|2013-2015
 
|2013-2015
 
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
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</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''SOLO1:''' Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian C, Bradley W, Mathews C, Liu J, Lowe ES, Bloomfield R, DiSilvestro P. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018 Dec 27;379(26):2495-2505. Epub 2018 Oct 21. [https://doi.org/10.1056/NEJMoa1810858 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30345884 PubMed] NCT01844986
+
# '''SOLO1:''' Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian C, Bradley W, Mathews C, Liu J, Lowe ES, Bloomfield R, DiSilvestro P. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018 Dec 27;379(26):2495-2505. Epub 2018 Oct 21. [https://doi.org/10.1056/NEJMoa1810858 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30345884/ PubMed] [https://clinicaltrials.gov/study/NCT01844986 NCT01844986]
 +
##'''Subgroup analysis:''' DiSilvestro P, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian CA, Bradley WH, Mathews CA, Liu J, Lowe ES, Bloomfield R, Moore KN. Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial. J Clin Oncol. 2020 Oct 20;38(30):3528-3537. Epub 2020 Aug 4. [https://doi.org/10.1200/jco.20.00799 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8190876/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32749942/ PubMed]
 
## '''HRQoL analysis:''' Friedlander M, Moore KN, Colombo N, Scambia G, Kim BG, Oaknin A, Lisyanskaya A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian C, Bradley WH, Liu J, Mathews C, Selle F, Lortholary A, Lowe ES, Hettle R, Flood E, Parkhomenko E, DiSilvestro P. Patient-centred outcomes and effect of disease progression on health status in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation receiving maintenance olaparib or placebo (SOLO1): a randomised, phase 3 trial. Lancet Oncol. 2021 May;22(5):632-642. Epub 2021 Apr 13. [https://doi.org/10.1016/s1470-2045(21)00098-x link to original article] [https://pubmed.ncbi.nlm.nih.gov/33862001/ PubMed]
 
## '''HRQoL analysis:''' Friedlander M, Moore KN, Colombo N, Scambia G, Kim BG, Oaknin A, Lisyanskaya A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian C, Bradley WH, Liu J, Mathews C, Selle F, Lortholary A, Lowe ES, Hettle R, Flood E, Parkhomenko E, DiSilvestro P. Patient-centred outcomes and effect of disease progression on health status in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation receiving maintenance olaparib or placebo (SOLO1): a randomised, phase 3 trial. Lancet Oncol. 2021 May;22(5):632-642. Epub 2021 Apr 13. [https://doi.org/10.1016/s1470-2045(21)00098-x link to original article] [https://pubmed.ncbi.nlm.nih.gov/33862001/ PubMed]
 
## '''Update:''' Banerjee S, Moore KN, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Oza A, González-Martín A, Aghajanian C, Bradley WH, Holmes E, Lowe ES, DiSilvestro P. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 Dec;22(12):1721-1731. Epub 2021 Oct 26. Erratum in: Lancet Oncol. 2021 Dec;22(12):e539. [https://doi.org/10.1016/s1470-2045(21)00531-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34715071/ PubMed]
 
## '''Update:''' Banerjee S, Moore KN, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Oza A, González-Martín A, Aghajanian C, Bradley WH, Holmes E, Lowe ES, DiSilvestro P. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 Dec;22(12):1721-1731. Epub 2021 Oct 26. Erratum in: Lancet Oncol. 2021 Dec;22(12):e539. [https://doi.org/10.1016/s1470-2045(21)00531-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34715071/ PubMed]
 
## '''Update:''' DiSilvestro P, Banerjee S, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Oza A, González-Martín A, Aghajanian C, Bradley W, Mathews C, Liu J, McNamara J, Lowe ES, Ah-See ML, Moore KN; SOLO1 Investigators. Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial. J Clin Oncol. 2023 Jan 20;41(3):609-617. Epub 2022 Sep 9. [https://doi.org/10.1200/jco.22.01549 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc9870219/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36082969/ PubMed]
 
## '''Update:''' DiSilvestro P, Banerjee S, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Oza A, González-Martín A, Aghajanian C, Bradley W, Mathews C, Liu J, McNamara J, Lowe ES, Ah-See ML, Moore KN; SOLO1 Investigators. Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial. J Clin Oncol. 2023 Jan 20;41(3):609-617. Epub 2022 Sep 9. [https://doi.org/10.1200/jco.22.01549 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc9870219/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36082969/ PubMed]
 +
==Olaparib & Bevacizumab {{#subobject:19ugz4|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:a75ug6|Variant=1}}===
 +
{| class="wikitable sortable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 +
{| 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://doi.org/10.1056/nejmoa1911361 Ray-Coquard et al. 2019 (PAOLA-1)]
 +
<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
 +
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-217-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
 +
|-
 +
|} -->
 +
|2015-2017
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 +
|[[#Bevacizumab_monotherapy|Bevacizumab]]
 +
| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 22.1 vs 16.6 mo<br>(HR 0.59, 95% CI 0.49-0.72)<br><br>Did not meet secondary endpoint of OS<sup>1</sup><br>Median OS: 56.5 vs 51.6 mo<br>(HR 0.92, 95% CI 0.76-1.12)
 +
|-
 +
|}
 +
''<sup>1</sup>Reported efficacy is based on the 2023 update.''<br>
 +
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. The FDA-recommended duration of bevacizumab treatment is 22 cycles (including the 6 cycles of combination chemotherapy).''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*Not specified, but presumably platinum doublet & bevacizumab x 6; olaparib is started between 3 and 9 weeks after last chemotherapy dose.
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Olaparib (Lynparza)]] 300 mg PO twice per day
 +
*[[Bevacizumab (Avastin)]] as follows:
 +
**Cycles 1 to 16: 15 mg/kg IV once on day 1
 +
'''21-day cycle for up to 35 cycles (2 years)'''
 +
</div></div>
 +
===References===
 +
# '''PAOLA-1:''' Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, Fujiwara K, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alía EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marmé F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2416-2428. [https://doi.org/10.1056/nejmoa1911361 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31851799/ PubMed] [https://clinicaltrials.gov/study/NCT02477644 NCT02477644]
 +
##'''Update:''' Ray-Coquard I, Leary A, Pignata S, Cropet C, González-Martín A, Marth C, Nagao S, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alia EM, Bogner G, Yoshida H, Lefeuvre-Plesse C, Buderath P, Mosconi AM, Lortholary A, Burges A, Medioni J, El-Balat A, Rodrigues M, Park-Simon TW, Dubot C, Denschlag D, You B, Pujade-Lauraine E, Harter P; PAOLA-1/ENGOT-ov25 investigators. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ann Oncol. 2023 Aug;34(8):681-692. Epub 2023 May 19. [https://doi.org/10.1016/j.annonc.2023.05.005 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37211045/ PubMed]
  
 
=Relapsed or recurrent disease, platinum-sensitive=
 
=Relapsed or recurrent disease, platinum-sensitive=
 +
==Carboplatin monotherapy {{#subobject:f19c03|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, q3wk {{#subobject:34cc91|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://doi.org/10.1200/jco.23.01225 Lorusso et al. 2024 (MITO-23)]
 +
|2016-04-21 to 2018-12-17
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Trabectedin_monotherapy_999|Trabectedin]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*BRCA1 or BRCA2 mutations or BRCAness phenotype
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 +
'''21-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, q4wk {{#subobject:85cc91|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://doi.org/10.1200/jco.23.01225 Lorusso et al. 2024 (MITO-23)]
 +
|2016-04-21 to 2018-12-17
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Trabectedin_monotherapy_999|Trabectedin]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*BRCA1 or BRCA2 mutations or BRCAness phenotype
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 +
'''28-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''MITO-23:''' Lorusso D, Raspagliesi F, Ronzulli D, Valabrega G, Colombo N, Pisano C, Cassani C, Tognon G, Tamberi S, Mangili G, Mammoliti S, De Giorgi U, Greco F, Mosconi AM, Breda E, Artioli G, Andreetta C, Casanova C, Ceccherini R, Frassoldati A, Salutari V, Giolitto S, Scambia G. Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial. J Clin Oncol. 2024 May 1;42(13):1488-1498. Epub 2024 Feb 5. [https://doi.org/10.1200/jco.23.01225 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/38315944/ PubMed] [https://clinicaltrials.gov/study/NCT02903004 NCT02903004]
 +
 +
==Gemcitabine monotherapy {{#subobject:f47gea|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:8meg3d|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/pmc7145583/ Penson et al. 2020 (SOLO3)]
 +
|2015-2018
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Olaparib_monotherapy_2|Olaparib]]
 +
| style="background-color:#fc8d59" |Seems to have inferior PFS
 +
|-
 +
|[https://doi.org/10.1200/jco.23.01225 Lorusso et al. 2024 (MITO-23)]
 +
|2016-04-21 to 2018-12-17
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Trabectedin_monotherapy_999|Trabectedin]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*SOLO3: Germline BRCA1 or BRCA2 mutations
 +
*MITO-23: BRCA1 or BRCA2 mutations or BRCAness phenotype
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
'''28-day cycles'''
 +
</div></div>
 +
 +
===References===
 +
#'''SOLO3:''' Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA 3rd, Bidziński M, Kim JW, Nam JH, Madry R, Hernández C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1164-1174. Epub 2020 Feb 19. [https://doi.org/10.1200/jco.19.02745 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7145583/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32073956/ PubMed] [https://clinicaltrials.gov/study/NCT02282020 NCT02282020]
 +
#'''MITO-23:''' Lorusso D, Raspagliesi F, Ronzulli D, Valabrega G, Colombo N, Pisano C, Cassani C, Tognon G, Tamberi S, Mangili G, Mammoliti S, De Giorgi U, Greco F, Mosconi AM, Breda E, Artioli G, Andreetta C, Casanova C, Ceccherini R, Frassoldati A, Salutari V, Giolitto S, Scambia G. Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial. J Clin Oncol. 2024 May 1;42(13):1488-1498. Epub 2024 Feb 5. [https://doi.org/10.1200/jco.23.01225 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/38315944/ PubMed] [https://clinicaltrials.gov/study/NCT02903004 NCT02903004]
 +
 
==Olaparib monotherapy {{#subobject:f47yha|Regimen=1}}==
 
==Olaparib monotherapy {{#subobject:f47yha|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
Line 68: Line 239:
 
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 
|Investigator's choice of:<br>1a. [[#Paclitaxel_monotherapy|Paclitaxel]]<br>1b. [[#Gemcitabine_monotherapy|Gemcitabine]]<br>1c. [[#Pegylated_liposomal_doxorubicin_monotherapy|PLD]]<br>1d. [[#Topotecan_monotherapy|Topotecan]]
 
|Investigator's choice of:<br>1a. [[#Paclitaxel_monotherapy|Paclitaxel]]<br>1b. [[#Gemcitabine_monotherapy|Gemcitabine]]<br>1c. [[#Pegylated_liposomal_doxorubicin_monotherapy|PLD]]<br>1d. [[#Topotecan_monotherapy|Topotecan]]
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 13.4 vs 9.2 mo<br>(HR 0.62, 95% CI 0.43-0.91)
+
| style="background-color:#91cf60" |Seems to have superior PFS (secondary endpoint)<br>Median PFS: 13.4 vs 9.2 mo<br>(HR 0.62, 95% CI 0.43-0.91)<br><br>Superior ORR (primary endpoint)
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#fdcdac">
 
<div class="toccolours" style="background-color:#fdcdac">
 
====Biomarker eligibility criteria====
 
====Biomarker eligibility criteria====
−
*Germline BRCA1/2 mutations
+
*Germline BRCA1 or BRCA2 mutations
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
Line 80: Line 251:
 
'''Continued indefinitely'''
 
'''Continued indefinitely'''
 
</div></div>
 
</div></div>
 +
 +
===References===
 +
#'''SOLO3:''' Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA 3rd, Bidziński M, Kim JW, Nam JH, Madry R, Hernández C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1164-1174. Epub 2020 Feb 19. [https://doi.org/10.1200/jco.19.02745 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7145583/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32073956/ PubMed] [https://clinicaltrials.gov/study/NCT02282020 NCT02282020]
 +
 +
==Paclitaxel monotherapy {{#subobject:f47paa|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, weekly {{#subobject:8tax0d|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/pmc7145583/ Penson et al. 2020 (SOLO3)]
 +
|2015-2018
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Olaparib_monotherapy_2|Olaparib]]
 +
| style="background-color:#fc8d59" |Seems to have inferior PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*Germline BRCA1 or BRCA2 mutations
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once on day 1
 +
'''7-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 3 out of 4 weeks {{#subobject:3cax0d|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://doi.org/10.1200/jco.23.01225 Lorusso et al. 2024 (MITO-23)]
 +
|2016-04-21 to 2018-12-17
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Trabectedin_monotherapy_999|Trabectedin]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*BRCA1 or BRCA2 mutations or BRCAness phenotype
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
'''28-day cycles'''
 +
</div></div>
 +
 +
===References===
 +
#'''SOLO3:''' Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA 3rd, Bidziński M, Kim JW, Nam JH, Madry R, Hernández C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1164-1174. Epub 2020 Feb 19. [https://doi.org/10.1200/jco.19.02745 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7145583/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32073956/ PubMed] [https://clinicaltrials.gov/study/NCT02282020 NCT02282020]
 +
#'''MITO-23:''' Lorusso D, Raspagliesi F, Ronzulli D, Valabrega G, Colombo N, Pisano C, Cassani C, Tognon G, Tamberi S, Mangili G, Mammoliti S, De Giorgi U, Greco F, Mosconi AM, Breda E, Artioli G, Andreetta C, Casanova C, Ceccherini R, Frassoldati A, Salutari V, Giolitto S, Scambia G. Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial. J Clin Oncol. 2024 May 1;42(13):1488-1498. Epub 2024 Feb 5. [https://doi.org/10.1200/jco.23.01225 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/38315944/ PubMed] [https://clinicaltrials.gov/study/NCT02903004 NCT02903004]
 +
 +
==Pegylated liposomal doxorubicin monotherapy {{#subobject:ftplda|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 40 mg/m<sup>2</sup> {{#subobject:pld43d|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://doi.org/10.1200/jco.23.01225 Lorusso et al. 2024 (MITO-23)]
 +
|2016-04-21 to 2018-12-17
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Trabectedin_monotherapy_999|Trabectedin]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*BRCA1 or BRCA2 mutations or BRCAness phenotype
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Pegylated liposomal doxorubicin (Doxil)]] 40 mg/m<sup>2</sup> IV once on day 1
 +
'''28-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 50 mg/m<sup>2</sup> {{#subobject:pld33d|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/pmc7145583/ Penson et al. 2020 (SOLO3)]
 +
|2015-2018
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Olaparib_monotherapy_2|Olaparib]]
 +
| style="background-color:#fc8d59" |Seems to have inferior PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*Germline BRCA1 or BRCA2 mutations
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Pegylated liposomal doxorubicin (Doxil)]] 50 mg/m<sup>2</sup> IV once on day 1
 +
'''28-day cycles'''
 +
</div></div>
 +
 +
===References===
 +
#'''SOLO3:''' Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA 3rd, Bidziński M, Kim JW, Nam JH, Madry R, Hernández C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1164-1174. Epub 2020 Feb 19. [https://doi.org/10.1200/jco.19.02745 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7145583/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32073956/ PubMed] [https://clinicaltrials.gov/study/NCT02282020 NCT02282020]
 +
#'''MITO-23:''' Lorusso D, Raspagliesi F, Ronzulli D, Valabrega G, Colombo N, Pisano C, Cassani C, Tognon G, Tamberi S, Mangili G, Mammoliti S, De Giorgi U, Greco F, Mosconi AM, Breda E, Artioli G, Andreetta C, Casanova C, Ceccherini R, Frassoldati A, Salutari V, Giolitto S, Scambia G. Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial. J Clin Oncol. 2024 May 1;42(13):1488-1498. Epub 2024 Feb 5. [https://doi.org/10.1200/jco.23.01225 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/38315944/ PubMed] [https://clinicaltrials.gov/study/NCT02903004 NCT02903004]
 +
 +
==Topotecan monotherapy {{#subobject:ftcj4ea|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:tocp3d|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/pmc7145583/ Penson et al. 2020 (SOLO3)]
 +
|2015-2018
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Olaparib_monotherapy_2|Olaparib]]
 +
| style="background-color:#fc8d59" |Seems to have inferior PFS
 +
|-
 +
|[https://doi.org/10.1200/jco.23.01225 Lorusso et al. 2024 (MITO-23)]
 +
|2016-04-21 to 2018-12-17
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Trabectedin_monotherapy_999|Trabectedin]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*SOLO3: Germline BRCA1 or BRCA2 mutations
 +
*MITO-23: BRCA1 or BRCA2 mutations or BRCAness phenotype
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Topotecan (Hycamtin)]] 4 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
 +
'''28-day cycles'''
 +
</div></div>
 +
 
===References===
 
===References===
−
#'''SOLO3:''' Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA 3rd, Bidziński M, Kim JW, Nam JH, Madry R, Hernández C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1164-1174. Epub 2020 Feb 19. [https://doi.org/10.1200/jco.19.02745 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7145583/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32073956 PubMed] NCT00628251
+
#'''SOLO3:''' Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA 3rd, Bidziński M, Kim JW, Nam JH, Madry R, Hernández C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1164-1174. Epub 2020 Feb 19. [https://doi.org/10.1200/jco.19.02745 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7145583/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32073956/ PubMed] [https://clinicaltrials.gov/study/NCT02282020 NCT02282020]
−
##'''Subgroup analysis:''' DiSilvestro P, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian CA, Bradley WH, Mathews CA, Liu J, Lowe ES, Bloomfield R, Moore KN. Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial. J Clin Oncol. 2020 Oct 20;38(30):3528-3537. Epub 2020 Aug 4. [https://doi.org/10.1200/jco.20.00799 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8190876/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32749942/ PubMed]
+
#'''MITO-23:''' Lorusso D, Raspagliesi F, Ronzulli D, Valabrega G, Colombo N, Pisano C, Cassani C, Tognon G, Tamberi S, Mangili G, Mammoliti S, De Giorgi U, Greco F, Mosconi AM, Breda E, Artioli G, Andreetta C, Casanova C, Ceccherini R, Frassoldati A, Salutari V, Giolitto S, Scambia G. Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial. J Clin Oncol. 2024 May 1;42(13):1488-1498. Epub 2024 Feb 5. [https://doi.org/10.1200/jco.23.01225 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/38315944/ PubMed] [https://clinicaltrials.gov/study/NCT02903004 NCT02903004]
 +
 
 
=Maintenance after second-line therapy for platinum-sensitive disease=
 
=Maintenance after second-line therapy for platinum-sensitive disease=
 
==Olaparib monotherapy {{#subobject:f4c078|Regimen=1}}==
 
==Olaparib monotherapy {{#subobject:f4c078|Regimen=1}}==
Line 95: Line 418:
 
|-
 
|-
 
|[https://doi.org/10.1016/S1470-2045(17)30469-2 Pujade-Lauraine et al. 2017 (SOLO2)]
 
|[https://doi.org/10.1016/S1470-2045(17)30469-2 Pujade-Lauraine et al. 2017 (SOLO2)]
−
{| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+
<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
 
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-145-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
 
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-145-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
 
|-
 
|-
−
|}
+
|} -->
−
|2013-2014
+
|2013-09-03 to 2014-11-21
 
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
|[[Ovarian_cancer_-_null_regimens#Placebo_2|Placebo]]
 
|[[Ovarian_cancer_-_null_regimens#Placebo_2|Placebo]]
Line 116: Line 439:
 
'''Continued indefinitely'''
 
'''Continued indefinitely'''
 
</div></div>
 
</div></div>
 +
 
===References===
 
===References===
 
<!-- # '''Abstract:''' Kathleen N. Moore, Paul DiSilvestro, Elizabeth S. Lowe, Sally Garnett, Eric Pujade-Lauraine. SOLO1 and SOLO2: Randomized phase III trials of olaparib in patients (pts) with ovarian cancer and a BRCA1/2 mutation (BRCAm). 2014 ASCO Annual Meeting abstract TPS5616. [http://meetinglibrary.asco.org/content/131636-144 link to abstract] -->
 
<!-- # '''Abstract:''' Kathleen N. Moore, Paul DiSilvestro, Elizabeth S. Lowe, Sally Garnett, Eric Pujade-Lauraine. SOLO1 and SOLO2: Randomized phase III trials of olaparib in patients (pts) with ovarian cancer and a BRCA1/2 mutation (BRCAm). 2014 ASCO Annual Meeting abstract TPS5616. [http://meetinglibrary.asco.org/content/131636-144 link to abstract] -->
−
# '''SOLO2:''' Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1274-1284. Epub 2017 Jul 25. [https://doi.org/10.1016/S1470-2045(17)30469-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28754483 PubMed] NCT01874353
+
# '''SOLO2:''' Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1274-1284. Epub 2017 Jul 25. [https://doi.org/10.1016/S1470-2045(17)30469-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28754483/ PubMed] [https://clinicaltrials.gov/study/NCT01874353 NCT01874353]
 
## '''Update:''' Poveda A, Floquet A, Ledermann JA, Asher R, Penson RT, Oza AM, Korach J, Huzarski T, Pignata S, Friedlander M, Baldoni A, Park-Simon TW, Tamura K, Sonke GS, Lisyanskaya A, Kim JH, Filho EA, Milenkova T, Lowe ES, Rowe P, Vergote I, Pujade-Lauraine E; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):620-631. Epub 2021 Mar 18. [https://doi.org/10.1016/s1470-2045(21)00073-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33743851/ PubMed]
 
## '''Update:''' Poveda A, Floquet A, Ledermann JA, Asher R, Penson RT, Oza AM, Korach J, Huzarski T, Pignata S, Friedlander M, Baldoni A, Park-Simon TW, Tamura K, Sonke GS, Lisyanskaya A, Kim JH, Filho EA, Milenkova T, Lowe ES, Rowe P, Vergote I, Pujade-Lauraine E; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):620-631. Epub 2021 Mar 18. [https://doi.org/10.1016/s1470-2045(21)00073-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33743851/ PubMed]
  
 
=Relapsed or recurrent disease, platinum-resistant=
 
=Relapsed or recurrent disease, platinum-resistant=
 
==Olaparib monotherapy {{#subobject:6ab358|Regimen=1}}==
 
==Olaparib monotherapy {{#subobject:6ab358|Regimen=1}}==
−
<div class="toccolours" style="background-color:#eeeeee">
+
<div class="toccolours" style="background-color:#ee6b6e">
 
===Regimen {{#subobject:5cec53|Variant=1}}===
 
===Regimen {{#subobject:5cec53|Variant=1}}===
 
{| class="wikitable" style="width: 60%; text-align:center;"  
 
{| class="wikitable" style="width: 60%; text-align:center;"  
Line 135: Line 459:
 
|-
 
|-
 
|[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)]
−
|2010-2012
+
|2010-02-21 to 2012-07-31
 
|style="background-color:#91cf61"|Phase 2 (RT)
 
|style="background-color:#91cf61"|Phase 2 (RT)
 
|-
 
|-
 
|}
 
|}
−
''Note: Patients in Study 42 were resistant to prior platinum-containing therapy.''
+
''Note: Patients in Study 42 had cancer that was resistant to prior platinum-containing therapy. The FDA indication supported by Study 42 was voluntarily withdrawn by the manufacturer in 2022.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*ICEBERG 2: BRCA1 or BRCA2 mutations
 +
*Study 42: Germline BRCA1 or BRCA2 mutations
 +
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<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 on days 1 to 28
−
'''Continued indefinitely'''
+
'''28-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''ICEBERG 2:''' Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel JN, Oaknin A, Loman N, Lu K, Schmutzler RK, Matulonis U, Wickens M, Tutt A. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010 Jul 24;376(9737):245-51. Epub 2010 Jul 6. [https://doi.org/10.1016/S0140-6736(10)60893-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20609468 PubMed] NCT00494442
+
# '''ICEBERG 2:''' Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel JN, Oaknin A, Loman N, Lu K, Schmutzler RK, Matulonis U, Wickens M, Tutt A. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010 Jul 24;376(9737):245-51. Epub 2010 Jul 6. [https://doi.org/10.1016/S0140-6736(10)60893-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20609468/ PubMed] [https://clinicaltrials.gov/study/NCT00494442 NCT00494442]
 
<!-- 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] '''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
+
# '''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] [https://clinicaltrials.gov/study/NCT01078662 NCT01078662]
 
## '''Subgroup analysis:''' Domchek SM, Aghajanian C, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Loman N, Robertson JD, Mann H, Kaufman B. Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy. Gynecol Oncol. 2016 Feb;140(2):199-203. Epub 2015 Dec 23. [https://doi.org/10.1016/j.ygyno.2015.12.020 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992984/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26723501/ PubMed]
 
## '''Subgroup analysis:''' Domchek SM, Aghajanian C, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Loman N, Robertson JD, Mann H, Kaufman B. Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy. Gynecol Oncol. 2016 Feb;140(2):199-203. Epub 2015 Dec 23. [https://doi.org/10.1016/j.ygyno.2015.12.020 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992984/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26723501/ PubMed]
 +
 
=Additional resources=
 
=Additional resources=
 
*[https://oncomx.org/searchview/?gene=BRCA1 OncoMX -- BRCA1]
 
*[https://oncomx.org/searchview/?gene=BRCA1 OncoMX -- BRCA1]

Revision as of 22:53, 28 May 2024

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Section editor
Brown-alaina.jpeg
 Alaina J. Brown, MD, MPH
Vanderbilt University
Nashville, TN, USA
LinkedIn
11 regimens on this page
14 variants on this page

Note: this page has regimens which are specific to ovarian cancer with homologous recombination deficiency (HRD). Please see the main ovarian cancer page for other chemotherapy 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.

ASCO

NCCN

Maintenance after first-line therapy

Bevacizumab monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Ray-Coquard et al. 2019 (PAOLA-1) 2015-2017 Phase 3 (C) Olaparib & Bevacizumab Inferior PFS

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. The FDA-recommended duration of treatment is 22 cycles (including the 6 cycles of combination chemotherapy).

Preceding treatment

  • Not specified, but presumably platinum doublet & bevacizumab x 6

Targeted therapy

21-day cycle for up to 16 cycles

References

  1. PAOLA-1: Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, Fujiwara K, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alía EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marmé F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2416-2428. link to original article contains dosing details in manuscript PubMed NCT02477644
    1. Update: Ray-Coquard I, Leary A, Pignata S, Cropet C, González-Martín A, Marth C, Nagao S, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alia EM, Bogner G, Yoshida H, Lefeuvre-Plesse C, Buderath P, Mosconi AM, Lortholary A, Burges A, Medioni J, El-Balat A, Rodrigues M, Park-Simon TW, Dubot C, Denschlag D, You B, Pujade-Lauraine E, Harter P; PAOLA-1/ENGOT-ov25 investigators. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ann Oncol. 2023 Aug;34(8):681-692. Epub 2023 May 19. link to original article PubMed

Olaparib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Moore et al. 2018 (SOLO1) 2013-2015 Phase 3 (E-RT-esc) Placebo Superior PFS1 (primary endpoint)
Median PFS: 56 vs 13.8 mo
(HR 0.33, 95% CI 0.25-0.43)

Superior OS2 (secondary endpoint)
OS84: 67% vs 46.5%
(HR 0.55, 95% CI 0.40-0.76)

1Reported efficacy for PFS is based on the 2021 update.
2Reported efficacy for OS is based on the 2022 update; the OS result did not meet the authors' predefined level of statistical significance, which was based on P-value.

Biomarker eligibility criteria

  • BRCA1 or BRCA2 mutations

Targeted therapy

Continued indefinitely

References

  1. SOLO1: Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian C, Bradley W, Mathews C, Liu J, Lowe ES, Bloomfield R, DiSilvestro P. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018 Dec 27;379(26):2495-2505. Epub 2018 Oct 21. link to original article contains dosing details in abstract PubMed NCT01844986
    1. Subgroup analysis: DiSilvestro P, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian CA, Bradley WH, Mathews CA, Liu J, Lowe ES, Bloomfield R, Moore KN. Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial. J Clin Oncol. 2020 Oct 20;38(30):3528-3537. Epub 2020 Aug 4. link to original article link to PMC article PubMed
    2. HRQoL analysis: Friedlander M, Moore KN, Colombo N, Scambia G, Kim BG, Oaknin A, Lisyanskaya A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian C, Bradley WH, Liu J, Mathews C, Selle F, Lortholary A, Lowe ES, Hettle R, Flood E, Parkhomenko E, DiSilvestro P. Patient-centred outcomes and effect of disease progression on health status in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation receiving maintenance olaparib or placebo (SOLO1): a randomised, phase 3 trial. Lancet Oncol. 2021 May;22(5):632-642. Epub 2021 Apr 13. link to original article PubMed
    3. Update: Banerjee S, Moore KN, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Oza A, González-Martín A, Aghajanian C, Bradley WH, Holmes E, Lowe ES, DiSilvestro P. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 Dec;22(12):1721-1731. Epub 2021 Oct 26. Erratum in: Lancet Oncol. 2021 Dec;22(12):e539. link to original article PubMed
    4. Update: DiSilvestro P, Banerjee S, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Oza A, González-Martín A, Aghajanian C, Bradley W, Mathews C, Liu J, McNamara J, Lowe ES, Ah-See ML, Moore KN; SOLO1 Investigators. Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial. J Clin Oncol. 2023 Jan 20;41(3):609-617. Epub 2022 Sep 9. link to original article link to PMC article PubMed

Olaparib & Bevacizumab

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Comparator Comparative Efficacy
Ray-Coquard et al. 2019 (PAOLA-1) 2015-2017 Phase 3 (E-RT-esc) Bevacizumab Superior PFS (primary endpoint)
Median PFS: 22.1 vs 16.6 mo
(HR 0.59, 95% CI 0.49-0.72)

Did not meet secondary endpoint of OS1
Median OS: 56.5 vs 51.6 mo
(HR 0.92, 95% CI 0.76-1.12)

1Reported efficacy is based on the 2023 update.
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. The FDA-recommended duration of bevacizumab treatment is 22 cycles (including the 6 cycles of combination chemotherapy).

Preceding treatment

  • Not specified, but presumably platinum doublet & bevacizumab x 6; olaparib is started between 3 and 9 weeks after last chemotherapy dose.

Targeted therapy

21-day cycle for up to 35 cycles (2 years)

References

  1. PAOLA-1: Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, Fujiwara K, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alía EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marmé F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2416-2428. link to original article contains dosing details in manuscript PubMed NCT02477644
    1. Update: Ray-Coquard I, Leary A, Pignata S, Cropet C, González-Martín A, Marth C, Nagao S, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alia EM, Bogner G, Yoshida H, Lefeuvre-Plesse C, Buderath P, Mosconi AM, Lortholary A, Burges A, Medioni J, El-Balat A, Rodrigues M, Park-Simon TW, Dubot C, Denschlag D, You B, Pujade-Lauraine E, Harter P; PAOLA-1/ENGOT-ov25 investigators. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ann Oncol. 2023 Aug;34(8):681-692. Epub 2023 May 19. link to original article PubMed

Relapsed or recurrent disease, platinum-sensitive

Carboplatin monotherapy

Regimen variant #1, q3wk

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Lorusso et al. 2024 (MITO-23) 2016-04-21 to 2018-12-17 Phase 3 (C) Trabectedin Did not meet primary endpoint of OS

Biomarker eligibility criteria

  • BRCA1 or BRCA2 mutations or BRCAness phenotype

Chemotherapy

21-day cycles


Regimen variant #2, q4wk

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Lorusso et al. 2024 (MITO-23) 2016-04-21 to 2018-12-17 Phase 3 (C) Trabectedin Did not meet primary endpoint of OS

Biomarker eligibility criteria

  • BRCA1 or BRCA2 mutations or BRCAness phenotype

Chemotherapy

28-day cycles

References

  1. MITO-23: Lorusso D, Raspagliesi F, Ronzulli D, Valabrega G, Colombo N, Pisano C, Cassani C, Tognon G, Tamberi S, Mangili G, Mammoliti S, De Giorgi U, Greco F, Mosconi AM, Breda E, Artioli G, Andreetta C, Casanova C, Ceccherini R, Frassoldati A, Salutari V, Giolitto S, Scambia G. Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial. J Clin Oncol. 2024 May 1;42(13):1488-1498. Epub 2024 Feb 5. link to original article contains dosing details in supplement PubMed NCT02903004

Gemcitabine monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Penson et al. 2020 (SOLO3) 2015-2018 Phase 3 (C) Olaparib Seems to have inferior PFS
Lorusso et al. 2024 (MITO-23) 2016-04-21 to 2018-12-17 Phase 3 (C) Trabectedin Did not meet primary endpoint of OS

Biomarker eligibility criteria

  • SOLO3: Germline BRCA1 or BRCA2 mutations
  • MITO-23: BRCA1 or BRCA2 mutations or BRCAness phenotype

Chemotherapy

28-day cycles

References

  1. SOLO3: Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA 3rd, Bidziński M, Kim JW, Nam JH, Madry R, Hernández C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1164-1174. Epub 2020 Feb 19. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02282020
  2. MITO-23: Lorusso D, Raspagliesi F, Ronzulli D, Valabrega G, Colombo N, Pisano C, Cassani C, Tognon G, Tamberi S, Mangili G, Mammoliti S, De Giorgi U, Greco F, Mosconi AM, Breda E, Artioli G, Andreetta C, Casanova C, Ceccherini R, Frassoldati A, Salutari V, Giolitto S, Scambia G. Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial. J Clin Oncol. 2024 May 1;42(13):1488-1498. Epub 2024 Feb 5. link to original article contains dosing details in supplement PubMed NCT02903004

Olaparib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Penson et al. 2020 (SOLO3) 2015-2018 Phase 3 (E-switch-ooc) Investigator's choice of:
1a. Paclitaxel
1b. Gemcitabine
1c. PLD
1d. Topotecan 		Seems to have superior PFS (secondary endpoint)
Median PFS: 13.4 vs 9.2 mo
(HR 0.62, 95% CI 0.43-0.91)

Superior ORR (primary endpoint)

Biomarker eligibility criteria

  • Germline BRCA1 or BRCA2 mutations

Targeted therapy

Continued indefinitely

References

  1. SOLO3: Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA 3rd, Bidziński M, Kim JW, Nam JH, Madry R, Hernández C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1164-1174. Epub 2020 Feb 19. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02282020

Paclitaxel monotherapy

Regimen variant #1, weekly

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Penson et al. 2020 (SOLO3) 2015-2018 Phase 3 (C) Olaparib Seems to have inferior PFS

Biomarker eligibility criteria

  • Germline BRCA1 or BRCA2 mutations

Chemotherapy

7-day cycles


Regimen variant #2, 3 out of 4 weeks

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Lorusso et al. 2024 (MITO-23) 2016-04-21 to 2018-12-17 Phase 3 (C) Trabectedin Did not meet primary endpoint of OS

Biomarker eligibility criteria

  • BRCA1 or BRCA2 mutations or BRCAness phenotype

Chemotherapy

28-day cycles

References

  1. SOLO3: Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA 3rd, Bidziński M, Kim JW, Nam JH, Madry R, Hernández C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1164-1174. Epub 2020 Feb 19. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02282020
  2. MITO-23: Lorusso D, Raspagliesi F, Ronzulli D, Valabrega G, Colombo N, Pisano C, Cassani C, Tognon G, Tamberi S, Mangili G, Mammoliti S, De Giorgi U, Greco F, Mosconi AM, Breda E, Artioli G, Andreetta C, Casanova C, Ceccherini R, Frassoldati A, Salutari V, Giolitto S, Scambia G. Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial. J Clin Oncol. 2024 May 1;42(13):1488-1498. Epub 2024 Feb 5. link to original article contains dosing details in supplement PubMed NCT02903004

Pegylated liposomal doxorubicin monotherapy

Regimen variant #1, 40 mg/m2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Lorusso et al. 2024 (MITO-23) 2016-04-21 to 2018-12-17 Phase 3 (C) Trabectedin Did not meet primary endpoint of OS

Biomarker eligibility criteria

  • BRCA1 or BRCA2 mutations or BRCAness phenotype

Chemotherapy

28-day cycles


Regimen variant #2, 50 mg/m2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Penson et al. 2020 (SOLO3) 2015-2018 Phase 3 (C) Olaparib Seems to have inferior PFS

Biomarker eligibility criteria

  • Germline BRCA1 or BRCA2 mutations

Chemotherapy

28-day cycles

References

  1. SOLO3: Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA 3rd, Bidziński M, Kim JW, Nam JH, Madry R, Hernández C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1164-1174. Epub 2020 Feb 19. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02282020
  2. MITO-23: Lorusso D, Raspagliesi F, Ronzulli D, Valabrega G, Colombo N, Pisano C, Cassani C, Tognon G, Tamberi S, Mangili G, Mammoliti S, De Giorgi U, Greco F, Mosconi AM, Breda E, Artioli G, Andreetta C, Casanova C, Ceccherini R, Frassoldati A, Salutari V, Giolitto S, Scambia G. Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial. J Clin Oncol. 2024 May 1;42(13):1488-1498. Epub 2024 Feb 5. link to original article contains dosing details in supplement PubMed NCT02903004

Topotecan monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Penson et al. 2020 (SOLO3) 2015-2018 Phase 3 (C) Olaparib Seems to have inferior PFS
Lorusso et al. 2024 (MITO-23) 2016-04-21 to 2018-12-17 Phase 3 (C) Trabectedin Did not meet primary endpoint of OS

Biomarker eligibility criteria

  • SOLO3: Germline BRCA1 or BRCA2 mutations
  • MITO-23: BRCA1 or BRCA2 mutations or BRCAness phenotype

Chemotherapy

28-day cycles

References

  1. SOLO3: Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA 3rd, Bidziński M, Kim JW, Nam JH, Madry R, Hernández C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1164-1174. Epub 2020 Feb 19. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02282020
  2. MITO-23: Lorusso D, Raspagliesi F, Ronzulli D, Valabrega G, Colombo N, Pisano C, Cassani C, Tognon G, Tamberi S, Mangili G, Mammoliti S, De Giorgi U, Greco F, Mosconi AM, Breda E, Artioli G, Andreetta C, Casanova C, Ceccherini R, Frassoldati A, Salutari V, Giolitto S, Scambia G. Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial. J Clin Oncol. 2024 May 1;42(13):1488-1498. Epub 2024 Feb 5. link to original article contains dosing details in supplement PubMed NCT02903004

Maintenance after second-line therapy for platinum-sensitive disease

Olaparib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pujade-Lauraine et al. 2017 (SOLO2) 2013-09-03 to 2014-11-21 Phase 3 (E-RT-esc) Placebo Superior PFS (primary endpoint)
Median PFS: 19.1 vs 5.5 mo
(HR 0.30, 95% CI 0.22-0.41)

Seems to have superior OS1 (secondary endpoint)
Median OS: 52 vs 39 mo
(HR 0.74, 95% CI 0.54-1.00)

1Reported efficacy is based on the 2021 update.
Patients had platinum-sensitive relapsed disease.

Biomarker eligibility criteria

  • BRCA1 or BRCA2 mutations

Targeted therapy

Continued indefinitely

References

  1. SOLO2: Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1274-1284. Epub 2017 Jul 25. link to original article contains dosing details in abstract PubMed NCT01874353
    1. Update: Poveda A, Floquet A, Ledermann JA, Asher R, Penson RT, Oza AM, Korach J, Huzarski T, Pignata S, Friedlander M, Baldoni A, Park-Simon TW, Tamura K, Sonke GS, Lisyanskaya A, Kim JH, Filho EA, Milenkova T, Lowe ES, Rowe P, Vergote I, Pujade-Lauraine E; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):620-631. Epub 2021 Mar 18. link to original article PubMed

Relapsed or recurrent disease, platinum-resistant

Olaparib monotherapy

Regimen

Study Dates of enrollment Evidence
Audeh et al. 2010 (ICEBERG 2) 2007-NR Phase 2
Kaufman et al. 2014 (Study 42) 2010-02-21 to 2012-07-31 Phase 2 (RT)

Note: Patients in Study 42 had cancer that was resistant to prior platinum-containing therapy. The FDA indication supported by Study 42 was voluntarily withdrawn by the manufacturer in 2022.

Biomarker eligibility criteria

  • ICEBERG 2: BRCA1 or BRCA2 mutations
  • Study 42: Germline BRCA1 or BRCA2 mutations

Targeted therapy

28-day cycles

References

  1. ICEBERG 2: Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel JN, Oaknin A, Loman N, Lu K, Schmutzler RK, Matulonis U, Wickens M, Tutt A. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010 Jul 24;376(9737):245-51. Epub 2010 Jul 6. link to original article contains dosing details in manuscript PubMed NCT00494442
  2. 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
    1. Subgroup analysis: Domchek SM, Aghajanian C, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Loman N, Robertson JD, Mann H, Kaufman B. Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy. Gynecol Oncol. 2016 Feb;140(2):199-203. Epub 2015 Dec 23. link to original article link to PMC article PubMed

Additional resources

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