Ovarian cancer, BRCA-mutated

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 Alaina J. Brown, MD, MPH
Vanderbilt University
Nashville, TN, USA
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4 regimens on this page
4 variants on this page

Note: this page has regimens which are specific to ovarian cancer that is BRCA-mutated. Please see the main ovarian cancer page for other chemotherapy regimens.


Guidelines

ASCO

NCCN

Maintenance after first-line therapy

Olaparib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Moore et al. 2018 (SOLO1)
ESMO-MCBS (4)
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. 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
    2. 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
    3. 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

Relapsed or recurrent disease, platinum-sensitive

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)

Biomarker eligibility criteria

  • Germline BRCA1/2 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 NCT00628251
    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

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)
ESMO-MCBS (4)
2013-2014 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) 2010-2012 Phase 2 (RT)

Note: Patients in Study 42 were resistant to prior platinum-containing therapy.

Targeted therapy

Continued indefinitely

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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