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Real-world experience of olaparib as maintenance therapy in BRCA-mutated recurrent ovarian cancer

Abstract

Purpose

The primary objective of our study was to investigate the effectiveness and safety of olaparib maintenance therapy in patients with BRCA-mutated recurrent ovarian cancer in daily practice. The secondary objective of this study was to identify prognostic factors associated with prolonged progression-free survival (PFS) in such patients.

Methods

We conducted a retrospective analysis of 40 patients who received olaparib maintenance treatment. Data on clinicopathological factors, oncological outcomes, and adverse events were obtained from medical records and analyzed.

Results

All patients had high-grade serous recurrent ovarian cancer with BRCA mutation and achieved complete or partial response to the most recent platinum-based chemotherapy. After a median follow-up of 14.3 months, the median PFS was 23.7 months (95% confidence interval, 14.1–33.4); however, the median overall survival was not reached. In the log-rank test, the PFS was significantly longer for patients with most recent platinum-free interval (PFI) ≥ 12 months, complete response to the last platinum-based chemotherapy, and less than three lines of previous chemotherapy (p = 0.005, p = 0.016, and p = 0.023, respectively). Most hematologic and non-hematologic adverse events were of grade 1 or 2, and the common adverse events were mostly related to myelosuppression.

Conclusion

Olaparib maintenance treatment in BRCA-mutated recurrent ovarian cancer is effective and safe in clinical practice. Most recent PFI, response to the last platinum-based chemotherapy, and the number of previous chemotherapy lines were associated with PFS in patients with BRCA-mutated recurrent ovarian cancer.

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References

  1. 1.

    Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, Gaudet MM, Jemal A, Siegel RL (2018) Ovarian cancer statistics, 2018. Cancer J Clin 68(4):284–296. https://doi.org/10.3322/caac.21456

    Article  Google Scholar 

  2. 2.

    Hanker LC, Loibl S, Burchardi N, Pfisterer J, Meier W, Pujade-Lauraine E, Ray-Coquard I, Sehouli J, Harter P, du Bois A, Ago, group Gs (2012) The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy. Ann Oncol 23(10):2605–2612. https://doi.org/10.1093/annonc/mds203

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Giannakeas V, Sopik V, Narod SA (2016) A model for ovarian cancer progression based on inherent resistance. Gynecol Oncol 142(3):484–489. https://doi.org/10.1016/j.ygyno.2016.06.014

    Article  PubMed  Google Scholar 

  4. 4.

    Laganà AS, Sofo V, Vitale SG, Triolo O (2016) Epithelial ovarian cancer inherent resistance: may the pleiotropic interaction between reduced immunosurveillance and drug-resistant cells play a key role? Gynecol Oncol Rep 18:57–58. https://doi.org/10.1016/j.gore.2016.09.004

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Laganà AS, Colonese F, Colonese E, Sofo V, Salmeri FM, Granese R, Chiofalo B, Ciancimino L, Triolo O (2015) Cytogenetic analysis of epithelial ovarian cancer’s stem cells: an overview on new diagnostic and therapeutic perspectives. Eur J Gynaecol Oncol 36(5):495–505

    PubMed  Google Scholar 

  6. 6.

    Barra F, Laganà AS, Ghezzi F, Casarin J, Ferrero S (2019) Nintedanib for advanced epithelial ovarian cancer: a change of perspective? Summary of evidence from a systematic review. Gynecol Obstet Invest 84(2):107–117. https://doi.org/10.1159/000493361

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Berek JS (2019) Berek and Novak’s gynecology, 16th edition. Wolters Kluwer Health.

  8. 8.

    Markman M, Liu PY, Wilczynski S, Monk B, Copeland LJ, Alvarez RD, Jiang C, Alberts D (2003) Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial. J Clin Oncol 21(13):2460–2465. https://doi.org/10.1200/jco.2003.07.013

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    De Placido S, Scambia G, Di Vagno G, Naglieri E, Lombardi AV, Biamonte R, Marinaccio M, Carteni G, Manzione L, Febbraro A, De Matteis A, Gasparini G, Valerio MR, Danese S, Perrone F, Lauria R, De Laurentiis M, Greggi S, Gallo C, Pignata S (2004) Topotecan compared with no therapy after response to surgery and carboplatin/paclitaxel in patients with ovarian cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) randomized study. J Clin Oncol 22(13):2635–2642. https://doi.org/10.1200/jco.2004.09.088

    Article  PubMed  Google Scholar 

  10. 10.

    Pfisterer J, Weber B, Reuss A, Kimmig R, du Bois A, Wagner U, Bourgeois H, Meier W, Costa S, Blohmer JU, Lortholary A, Olbricht S, Stahle A, Jackisch C, Hardy-Bessard AC, Mobus V, Quaas J, Richter B, Schroder W, Geay JF, Luck HJ, Kuhn W, Meden H, Nitz U, Pujade-Lauraine E (2006) Randomized phase III trial of topotecan following carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a gynecologic cancer intergroup trial of the AGO-OVAR and GINECO. J Natl Cancer Inst 98(15):1036–1045. https://doi.org/10.1093/jnci/djj296

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX (2011) Incorporation of Bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365(26):2473–2483. https://doi.org/10.1056/NEJMoa1104390

    CAS  Article  Google Scholar 

  12. 12.

    Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, Bois Ad, Sehouli J, Kimmig R, Stähle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MKB, Oza AM (2011) A phase 3 trial of Bevacizumab in ovarian cancer. N Engl J Med 365(26):2484–2496. https://doi.org/10.1056/NEJMoa1103799

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, Kim B-G, Fujiwara K, Tewari KS, O’Malley DM, Davidson SA, Rubin SC, DiSilvestro P, Basen-Engquist K, Huang H, Chan JK, Spirtos NM, Ashfaq R, Mannel RS (2017) Bevacizumab and paclitaxel–carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 18(6):779–791. https://doi.org/10.1016/S1470-2045(17)30279-6

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR (2012) OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol 30(17):2039–2045. https://doi.org/10.1200/JCO.2012.42.0505

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I (2014) Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized Phase III trial. Obstet Gynecol Surv 69(7):402–404. https://doi.org/10.1097/01.ogx.0000452705.82050.e4

    Article  Google Scholar 

  16. 16.

    Oza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Park-Simon TW, Rustin G, Joly F, Mirza MR, Plante M, Quinn M, Poveda A, Jayson GC, Stark D, Swart AM, Farrelly L, Kaplan R, Parmar MK, Perren TJ (2015) Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol 16(8):928–936. https://doi.org/10.1016/s1470-2045(15)00086-8

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Tewari KS, Burger RA, Enserro D, Norquist BM, Swisher EM, Brady MF, Bookman MA, Fleming GF, Huang H, Homesley HD, Fowler JM, Greer BE, Boente M, Liang SX, Ye C, Bais C, Randall LM, Chan JK, Ferriss JS, Coleman RL, Aghajanian C, Herzog TJ, DiSaia PJ, Copeland LJ, Mannel RS, Birrer MJ, Monk BJ (2019) Final overall survival of a randomized trial of Bevacizumab for primary treatment of ovarian cancer. J Clin Oncol 37(26):2317–2328. https://doi.org/10.1200/jco.19.01009

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Aghajanian C, Goff B, Nycum LR, Wang YV, Husain A, Blank SV (2015) Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol 139(1):10–16. https://doi.org/10.1016/j.ygyno.2015.08.004

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Macpherson E, Watkins C, Carmichael J, Matulonis U (2012) Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 366(15):1382–1392. https://doi.org/10.1056/NEJMoa1105535

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    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 (2017) 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 18(9):1274–1284. https://doi.org/10.1016/s1470-2045(17)30469-2

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O’Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA (2017) Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390(10106):1949–1961. https://doi.org/10.1016/s0140-6736(17)32440-6

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Mądry R, Christensen RD, Berek JS, Dørum A, Tinker AV, du Bois A, González-Martín A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA (2016) Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med 375(22):2154–2164. https://doi.org/10.1056/NEJMoa1611310

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, Okamoto A, Moore KN, Efrat Ben-Baruch N, Werner TL, Cloven NG, Oaknin A, DiSilvestro PA, Morgan MA, Nam J-H, Leath CA, Nicum S, Hagemann AR, Littell RD, Cella D, Baron-Hay S, Garcia-Donas J, Mizuno M, Bell-McGuinn K, Sullivan DM, Bach BA, Bhattacharya S, Ratajczak CK, Ansell PJ, Dinh MH, Aghajanian C, Bookman MA (2019) Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med 381(25):2403–2415. https://doi.org/10.1056/NEJMoa1909707

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247. https://doi.org/10.1016/j.ejca.2008.10.026

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    National Cancer Institute Common terminology criteria for adverse events v4.0. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/Archive/CTCAE_4.0_2009-05-29_QuickReference_8.5x11.pdf

  26. 26.

    Ame JC, Spenlehauer C, de Murcia G (2004) The PARP superfamily. Bio Essays 26(8):882–893. https://doi.org/10.1002/bies.20085

    CAS  Article  Google Scholar 

  27. 27.

    Ashworth A (2008) A synthetic Lethal therapeutic approach: poly (ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol 26(22):3785–3790. https://doi.org/10.1200/jco.2008.16.0812

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Mullen MM, Kuroki LM, Thaker PH (2019) Novel treatment options in platinum-sensitive recurrent ovarian cancer: a review. Gynecol Oncol 152(2):416–425. https://doi.org/10.1016/j.ygyno.2018.10.023

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Copeland LJ, Brady MF, Burger RA, Rodgers WH, Huang H, Cella D, Fowler JM, Walker JL, Tewari KS, Bender DP, Morris RT, Lowery WJ, Miller DS, Dewdney SB, Spirtos NM, Lele SB, Guntupalli SR, Ueland FR, Glaser GE, Mannel RS, DiSaia PJ (2017) A phase III trial of maintenance therapy in women with advanced ovarian/fallopian tube/peritoneal cancer after a complete clinical response to first-line therapy: an NRG oncology study. Gynecol Oncol 145:219. https://doi.org/10.1016/j.ygyno.2017.03.504

    Article  Google Scholar 

  30. 30.

    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, Gonzalez-Martin A, Aghajanian C, Bradley W, Mathews C, Liu J, Lowe ES, Bloomfield R, DiSilvestro P (2018) Maintenance Olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 379(26):2495–2505. https://doi.org/10.1056/NEJMoa1810858

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Cecere SC, Giannone G, Salutari V, Arenare L, Lorusso D, Ronzino G, Lauria R, Cormio G, Carella C, Scollo P, Ghizzoni V, Raspagliesi F, Di Napoli M, Mazzoni E, Marchetti C, Bergamini A, Orditura M, Valabrega G, Scambia G, Maltese G, De Matteis E, Cardalesi C, Loizzi V, Boccia S, Naglieri E, Scandurra G, Pignata S (2020) Olaparib as maintenance therapy in patients with BRCA 1–2 mutated recurrent platinum sensitive ovarian cancer: real world data and post progression outcome. Gynecol Oncol 156(1):38–44. https://doi.org/10.1016/j.ygyno.2019.10.023

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Labidi-Galy SI, de La Motte RT, Derbel O, Wolfer A, Kalbacher E, Olivier T, Combes JD, Heimgartner-Hu K, Tredan O, Guevara H, Heudel PE, Reverdy T, Bazan F, Heinzelmann-Schwarz V, Fehr M, de Castelbajac V, Vaflard P, Crivelli L, Bonadona V, Viassolo V, Buisson A, Golmard L, Rodrigues M, Ray-Coquard I (2019) Clinical factors associated with prolonged response and survival under olaparib as maintenance therapy in BRCA mutated ovarian cancers. Gynecol Oncol 155(2):262–269. https://doi.org/10.1016/j.ygyno.2019.09.008

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Paik ES, Lee YJ, Lee JY, Shin W, Park SY, Kim SI, Kim JW, Choi CH (2019) Kim BG (2019) Real-world experience of Olaparib maintenance in high-grade serous recurrent ovarian cancer patients with BRCA1/2 mutation: a Korean multicenter study. J Clin Med. 8(11):1920. https://doi.org/10.3390/jcm8111920

    CAS  Article  PubMed Central  Google Scholar 

  34. 34.

    Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott CL, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Dougherty B, Orr M, Hodgson D, Barrett JC, Matulonis U (2014) Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol 15(8):852–861. https://doi.org/10.1016/s1470-2045(14)70228-1

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    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 (2016) 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 140(2):199–203. https://doi.org/10.1016/j.ygyno.2015.12.020

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, Rimel BJ, Buss MK, Nattam SR, Hurteau J, Luo W, Curtis J, Whalen C, Kohn EC, Ivy SP, Matulonis UA (2019) Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer. Ann Oncol 30(4):551–557. https://doi.org/10.1093/annonc/mdz018

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Vitale SG, Capriglione S, Zito G, Lopez S, Gulino FA, Di Guardo F, Vitagliano A, Noventa M, La Rosa VL, Sapia F, Valenti G, Rapisarda AMC, Peterlunger I, Rossetti D, Laganà AS (2019) Management of endometrial, ovarian and cervical cancer in the elderly: current approach to a challenging condition. Arch Gynecol Obstet 299(2):299–315. https://doi.org/10.1007/s00404-018-5006-z

    Article  PubMed  Google Scholar 

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Authors

Contributions

AC contributed to data collection, data analysis, and manuscript writing. JYP developed the project, analyzed the data, and edited the manuscript. SWL, DYK, DSS, JHK, YMK, and YTK collected the data and edited the manuscript.

Corresponding author

Correspondence to Jeong-Yeol Park.

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The authors declare that they have no conflict of interest.

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This study was approved by the institutional review board of Asan Medical Center (2020–0051).

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The study used previously collected/existing clinical data and medical records; therefore, the need for informed consent was waived by the institutional review board of Asan Medical Center.

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Cho, A., Park, JY., Lee, SW. et al. Real-world experience of olaparib as maintenance therapy in BRCA-mutated recurrent ovarian cancer. Arch Gynecol Obstet 304, 1055–1063 (2021). https://doi.org/10.1007/s00404-021-06013-x

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Keywords

  • Ovarian cancer
  • Maintenance therapy
  • Olaparib
  • BRCA mutation