Ovarian cancer, HRD-positive

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Last updated on 2024-07-23:11 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), including those with germline or somatic BRCA1/2 mutations. 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==
*2022: Tew et al. Poly(ADP-Ribose) Polymerase Inhibitors in the Management of Ovarian Cancer: ASCO Guideline Rapid Recommendation Update EuroPMC
**2020: Tew et al. PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline link to PMC article EuroPMC
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Ovarian Cancer, Including Fallopian Tube Cancer and Primary Peritoneal Cancer.
=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	Shorter 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====
*Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for up to 16 cycles
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC 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. link to original article EuroPMC
==Olaparib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Moore et al. 2018 (SOLO1)	2013-2015 	Phase 3 (E-RT-esc)	Placebo 	Longer PFS1 (primary endpoint)Median PFS: 56 vs 13.8 mo(HR 0.33, 95% CI 0.25-0.43)Longer 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====
*Olaparib (Lynparza) 300 mg PO twice per day
Continued indefinitely
===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. link to original article dosing details in abstract have been reviewed by our editors EuroPMC 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. link to original article link to PMC article EuroPMC
## 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 EuroPMC
## 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 EuroPMC
## 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 EuroPMC
==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	Longer 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 OS1Median 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====
*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)
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC 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. link to original article EuroPMC
=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 OSMedian OS: 17.9 vs 15.8 mo(HR 0.87, 95% CI 0.66-1.14)
====Biomarker eligibility criteria====
*BRCA1 or BRCA2 mutations or BRCAness phenotype
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
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 OSMedian OS: 17.9 vs 15.8 mo(HR 0.87, 95% CI 0.66-1.14)
====Biomarker eligibility criteria====
*BRCA1 or BRCA2 mutations or BRCAness phenotype
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
28-day cycles
===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. link to original article dosing details in supplement have been reviewed by our editors EuroPMC 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 shorter PFSMedian PFS: 9.2 vs 13.4 mo(HR 1.61, 95% CI 1.10-2.33)
Lorusso et al. 2024 (MITO-23)	2016-04-21 to 2018-12-17	Phase 3 (C)	Trabectedin	Did not meet primary endpoint of OSMedian OS: 17.9 vs 15.8 mo(HR 0.87, 95% CI 0.66-1.14)
====Biomarker eligibility criteria====
*SOLO3: Germline BRCA1 or BRCA2 mutations
*MITO-23: BRCA1 or BRCA2 mutations or BRCAness phenotype
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
===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. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC 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. link to original article dosing details in supplement have been reviewed by our editors EuroPMC 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. Paclitaxel1b. Gemcitabine1c. PLD1d. Topotecan	Seems to have longer PFS (secondary endpoint)Median PFS: 13.4 vs 9.2 mo(HR 0.62, 95% CI 0.43-0.91)Higher ORR (primary endpoint)
====Biomarker eligibility criteria====
*Germline BRCA1 or BRCA2 mutations
====Targeted therapy====
*Olaparib (Lynparza) 300 mg PO twice per day
Continued indefinitely
===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. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC 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 shorter PFSMedian PFS: 9.2 vs 13.4 mo(HR 1.61, 95% CI 1.10-2.33)
====Biomarker eligibility criteria====
*Germline BRCA1 or BRCA2 mutations
====Chemotherapy====
*Paclitaxel (Taxol) 80 mg/m2 IV once on day 1
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 OSMedian OS: 17.9 vs 15.8 mo(HR 0.87, 95% CI 0.66-1.14)
====Biomarker eligibility criteria====
*BRCA1 or BRCA2 mutations or BRCAness phenotype
====Chemotherapy====
*Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
===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. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC 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. link to original article dosing details in supplement have been reviewed by our editors EuroPMC 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 OSMedian OS: 17.9 vs 15.8 mo(HR 0.87, 95% CI 0.66-1.14)
====Biomarker eligibility criteria====
*BRCA1 or BRCA2 mutations or BRCAness phenotype
====Chemotherapy====
*Pegylated liposomal doxorubicin (Doxil) 40 mg/m2 IV once on day 1
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 shorter PFSMedian PFS: 9.2 vs 13.4 mo(HR 1.61, 95% CI 1.10-2.33)
====Biomarker eligibility criteria====
*Germline BRCA1 or BRCA2 mutations
====Chemotherapy====
*Pegylated liposomal doxorubicin (Doxil) 50 mg/m2 IV once on day 1
28-day cycles
===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. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC 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. link to original article dosing details in supplement have been reviewed by our editors EuroPMC 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 shorter PFSMedian PFS: 9.2 vs 13.4 mo(HR 1.61, 95% CI 1.10-2.33)
Lorusso et al. 2024 (MITO-23)	2016-04-21 to 2018-12-17	Phase 3 (C)	Trabectedin	Did not meet primary endpoint of OSMedian OS: 17.9 vs 15.8 mo(HR 0.87, 95% CI 0.66-1.14)
====Biomarker eligibility criteria====
*SOLO3: Germline BRCA1 or BRCA2 mutations
*MITO-23: BRCA1 or BRCA2 mutations or BRCAness phenotype
====Chemotherapy====
*Topotecan (Hycamtin) 4 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
===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. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC 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. link to original article dosing details in supplement have been reviewed by our editors EuroPMC 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 	Longer PFS (primary endpoint)Median PFS: 19.1 vs 5.5 mo(HR 0.30, 95% CI 0.22-0.41)Seems to have longer 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====
*Olaparib (Lynparza) 300 mg PO twice per day
Continued indefinitely
===References===
# 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 dosing details in abstract have been reviewed by our editors EuroPMC NCT01874353
##HRQoL analysis: Friedlander M, Gebski V, Gibbs E, Davies L, Bloomfield R, Hilpert F, Wenzel LB, Eek D, Rodrigues M, Clamp A, Penson RT, Provencher D, Korach J, Huzarski T, Vidal L, Salutari V, Scott C, Nicoletto MO, Tamura K, Espinoza D, Joly F, Pujade-Lauraine E. Health-related quality of life and patient-centred outcomes with olaparib maintenance after chemotherapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT Ov-21): a placebo-controlled, phase 3 randomised trial. Lancet Oncol. 2018 Aug;19(8):1126-1134. Epub 2018 Jul 17. link to original article link to PMC article EuroPMC
## 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 EuroPMC
=Relapsed or recurrent disease, platinum-resistant=
==Olaparib monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Audeh et al. 2010 (ICEBERG 2) 	2007 to not reported 	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====
*Olaparib (Lynparza) 400 mg PO twice per day on days 1 to 28
28-day cycles
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00494442
# 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 EuroPMC 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. link to original article link to PMC article EuroPMC
=Additional resources=
*OncoMX -- BRCA1
*OncoMX -- BRCA2
Category:Ovarian cancer regimens
Category:Biomarker-specific pages
Category:Gynecologic cancers