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Personalized Treatment in Ovarian Cancer

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Personalization in Gynecologic Oncology

Part of the book series: Comprehensive Gynecology and Obstetrics ((CGO))

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Abstract

Ovarian cancer (OC) is a deadly gynecological malignancy, as the majority of patients are diagnosed at advanced stages. In recent years, the development and clinical application of molecularly targeted therapies such as bevacizumab (Bev), poly ADP-ribose polymerase (PARP) inhibitors, and anti-programmed cell death (PD)-1 antibodies may offer potentially beneficial treatment options for patients with advanced OC. However, the clinical utility of these therapies remains limited because they are associated with specific molecular abnormalities. Therefore, the identification of reliable molecular biomarkers is necessary for appropriate patient selection for these new treatment strategies. In this review, we outline the rationale for the selection of novel targets in advanced OC and discuss new therapeutic strategies that can be positioned as precision medicine for patients with advanced OC based on their broad mechanisms of action.

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References

  1. Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473–83.

    Article  CAS  PubMed  Google Scholar 

  2. Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365:2484–96.

    Article  CAS  PubMed  Google Scholar 

  3. Tewari KS, Burger RA, Enserro D, Norquist BM, Swisher EM, Brady MF, et al. Final overall survival of a randomized trial of bevacizumab for primary treatment of ovarian cancer. J Clin Oncol. 2019;37:2317–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Oza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E, et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomized trial. Lancet Oncol. 2015;16:928–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, et al. 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. 2012;30:2039–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Aghajanian C, Goff B, Nycum LR, Wang YV, Husain A, Blank SV. 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. 2015;139:10–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, et al. 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. 2017;18:779–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Pfisterer J, Shannon CM, Baumann K, Rau J, Harter P, Joly F, et al. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Lancet Oncol. 2020;21:699–709.

    Article  CAS  PubMed  Google Scholar 

  9. Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, et al. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021;22:267–76.

    Article  CAS  PubMed  Google Scholar 

  10. Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol. 2014;32:1302–8.

    Article  CAS  PubMed  Google Scholar 

  11. Bais C, Mueller B, Brady MF, Mannel RS, Burger RA, Wei W, et al. Tumor microvessel density as a potential predictive marker for bevacizumab benefit: GOG-0218 biomarker analyses. J Natl Cancer Inst. 2017;109:djx066.

    Article  PubMed Central  Google Scholar 

  12. Alvarez Secord A, Bell Burdett K, Owzar K, Tritchler D, Sibley AB, Liu Y, et al. Predictive blood-based biomarkers in patients with epithelial ovarian cancer treated with carboplatin and paclitaxel with or without bevacizumab: results from GOG-0218. Clin Cancer Res. 2020;26:1288–96.

    Article  PubMed  Google Scholar 

  13. Collinson F, Hutchinson M, Craven RA, Cairns DA, Zougman A, Wind TC, et al. Predicting response to bevacizumab in ovarian cancer: a panel of potential biomarkers informing treatment selection. Clin Cancer Res. 2013;19:5227–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Norquist BM, Brady MF, Harrell MI, Walsh T, Lee MK, Gulsuner S, et al. Mutations in homologous recombination genes and outcomes in ovarian carcinoma patients in GOG 218: an NRG oncology/gynecologic oncology group study. Clin Cancer Res. 2018;24:777–83.

    Article  CAS  PubMed  Google Scholar 

  15. Ferriss JS, Java JJ, Bookman MA, Fleming GF, Monk BJ, Walker JL, et al. Ascites predicts treatment benefit of bevacizumab in front-line therapy of advanced epithelial ovarian, fallopian tube and peritoneal cancers: an NRG oncology/GOG study. Gynecol Oncol. 2015;139:17–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wade KNS, Brady MF, Thai T, Wang Y, Zheng B, Salani R, et al. Measurements of adiposity as prognostic biomarkers for survival with anti-angiogenic treatment in epithelial ovarian cancer: an NRG oncology/gynecologic oncology group ancillary data analysis of GOG 218. Gynecol Oncol. 2019;155:69–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Buechel ME, Enserro D, Burger RA, Brady MF, Wade K, Secord AA, et al. Correlation of imaging and plasma based biomarkers to predict response to bevacizumab in epithelial ovarian cancer (OC). Gynecol Oncol. 2021;161:382–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. O’Connor MJ. Targeting the DNA damage response in cancer. Mol Cell. 2015;60:547–60.

    Article  PubMed  Google Scholar 

  19. Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, et al. Maintenance Olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379:2495–505.

    Article  CAS  PubMed  Google Scholar 

  20. Banerjee S, Moore KN, Colombo N, Scambia G, Kim BG, Oaknin A, et al. 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;22:1721–31.

    Article  CAS  PubMed  Google Scholar 

  21. DiSilvestro P, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, et al. 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;38:3528–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ray-Coquard I, Pautier P, Pignata S, Perol D, Gonzalez-Martin A, Berger R, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381:2416–28.

    Article  CAS  PubMed  Google Scholar 

  23. Harter P, Mouret-Reynier MA, Pignata S, Cropet C, Gonzalez-Martin A, Bogner G, et al. Efficacy of maintenance olaparib plus bevacizumab according to clinical risk in patients with newly diagnosed, advanced ovarian cancer in the phase III PAOLA-1/ENGOT-ov25 trial. Gynecol Oncol. 2022;164:254–64.

    Article  CAS  PubMed  Google Scholar 

  24. Gonzalez-Martin A, Pothuri B, Vergote I, DePont CR, Graybill W, Mirza MR, et al. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019;381:2391–402.

    Article  CAS  PubMed  Google Scholar 

  25. Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, et al. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med. 2019;381:2403–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tew WP, Lacchetti C, Ellis A, Maxian K, Banerjee S, Bookman M, et al. PARP inhibitors in the Management of Ovarian Cancer: ASCO guideline. J Clin Oncol. 2020;38:3468–93.

    Article  PubMed  Google Scholar 

  27. Vergote I, Ray-Coquard I, Anderson DM, Cantuaria G, Colombo N, Garnier-Tixidre C, et al. Population-adjusted indirect treatment comparison of the SOLO1 and PAOLA-1/ENGOT-ov25 trials evaluating maintenance olaparib or bevacizumab or the combination of both in newly diagnosed, advanced BRCA-mutated ovarian cancer. Eur J Cancer. 2021;157:415–23.

    Article  CAS  PubMed  Google Scholar 

  28. Murai J, Huang S-YN, Renaud A, Zhang Y, Ji J, Takeda S, et al. Stereospecific PARP trapping by BMN 673 and comparison with Olaparib and Rucaparib. Mol Cancer Ther. 2014;13:433–43.

    Article  CAS  PubMed  Google Scholar 

  29. Sun K, Mikule K, Wang Z, Poon G, Vaidyanathan A, Smith G, et al. A comparative pharmacokinetic study of PARP inhibitors demonstrates favorable properties for niraparib efficacy in preclinical tumor models. Oncotarget. 2018;9:37080–96.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012;366:1382–92.

    Article  CAS  PubMed  Google Scholar 

  31. Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol. 2016;17:1579–89.

    Article  CAS  PubMed  Google Scholar 

  32. Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, et al. 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;18:1274–84.

    Article  CAS  PubMed  Google Scholar 

  33. Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016;375:2154–64.

    Article  CAS  PubMed  Google Scholar 

  34. Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:1949–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA 3rd, Bidzinski M, et al. 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;38:1164–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Moore KN, Secord AA, Geller MA, Miller DS, Cloven N, Fleming GF, et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019;20:636–48.

    Article  CAS  PubMed  Google Scholar 

  37. Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun J, et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017;18:75–87.

    Article  CAS  PubMed  Google Scholar 

  38. Kristeleit R, Shapiro GI, Burris HA, Oza AM, LoRusso P, Patel MR, et al. A phase I-II study of the Oral PARP inhibitor Rucaparib in patients with germline BRCA1/2-mutated ovarian carcinoma or other solid tumors. Clin Cancer Res. 2017;23:4095–106.

    Article  CAS  PubMed  Google Scholar 

  39. Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348:203–13.

    Article  CAS  PubMed  Google Scholar 

  40. Hamanishi J, Mandai M, Ikeda T, Minami M, Kawaguchi A, Murayama T, et al. Safety and antitumor activity of anti-PD-1 antibody, Nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2015;33:4015–22.

    Article  CAS  PubMed  Google Scholar 

  41. Hamanishi J, Takeshima N, Katsumata N, Ushijima K, Kimura T, Takeuchi S, et al. Nivolumab versus gemcitabine or Pegylated liposomal doxorubicin for patients with platinum-resistant ovarian cancer: open-label, randomized trial in Japan (NINJA). J Clin Oncol. 2021;39:3671–81.

    Article  CAS  PubMed  Google Scholar 

  42. Monk BJ, Coleman RL, Fujiwara K, Wilson MK, Oza AM, Oaknin A, et al. ATHENA (GOG-3020/ENGOT-ov45): a randomized, phase III trial to evaluate rucaparib as monotherapy (ATHENA-MONO) and rucaparib in combination with nivolumab (ATHENA-COMBO) as maintenance treatment following frontline platinum-based chemotherapy in ovarian cancer. Int J Gynecol Cancer. 2021;31:1589–94.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Matulonis UA, Shapira-Frommer R, Santin AD, Lisyanskaya AS, Pignata S, Vergote I, et al. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Ann Oncol. 2019;30:1080–7.

    Article  CAS  PubMed  Google Scholar 

  44. Konstantinopoulos PA, Waggoner S, Vidal GA, Mita M, Moroney JW, Holloway R, et al. Single-arm phases 1 and 2 trial of Niraparib in combination with Pembrolizumab in patients with recurrent platinum-resistant ovarian carcinoma. JAMA Oncol. 2019;5:1141–9.

    Article  PubMed  PubMed Central  Google Scholar 

  45. https://clinicaltrials.gov/ct2/show/NCT03740165

  46. Pujade-Lauraine E, Fujiwara K, Ledermann JA, Oza AM, Kristeleit R, Ray-Coquard IL, et al. Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN ovarian 200): an open-label, three-arm, randomised, phase 3 study. Lancet Oncol. 2021;22:1034–46.

    Article  CAS  PubMed  Google Scholar 

  47. Monk BJ, Colombo N, Oza AM, Fujiwara K, Birrer MJ, Randall L, et al. Chemotherapy with or without avelumab followed by avelumab maintenance versus chemotherapy alone in patients with previously untreated epithelial ovarian cancer (JAVELIN ovarian 100): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22:1275–89.

    Article  CAS  PubMed  Google Scholar 

  48. Domchek SM, Postel-Vinay S, Im SA, Park YH, Delord JP, Italiano A, et al. Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Lancet Oncol. 2020;21:1155–64.

    Article  CAS  PubMed  Google Scholar 

  49. https://clinicaltrials.gov/ct2/show/NCT03737643

  50. Moore KN, Bookman M, Sehouli J, Miller A, Anderson C, Scambia G, et al. Atezolizumab, bevacizumab, and chemotherapy for newly diagnosed stage III or IV ovarian cancer: placebo-controlled randomized phase III trial (IMagyn050/GOG 3015/ENGOT-OV39). J Clin Oncol. 2021;39:1842–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Martin-Sabroso C, Lozza I, Torres-Suarez AI, Fraguas-Sanchez AI. Antibody-antineoplastic conjugates in gynecological malignancies: current status and future perspectives. Pharmaceutics. 2021;13:1705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. O’Malley DM, Calo CA. Progress in gynecologic cancers with antibody drug conjugates. Curr Oncol Rep. 2021;23:89.

    Article  PubMed  Google Scholar 

  53. Hafeez U, Parakh S, Gan HK, Scott AM. Antibody-drug conjugates for cancer therapy. Molecules. 2020;25:4764.

    Article  CAS  PubMed Central  Google Scholar 

  54. Erickson BK, Zeybek B, Santin AD, Fader AN. Targeting human epidermal growth factor receptor 2 (HER2) in gynecologic malignancies. Curr Opin Obstet Gynecol. 2020;32:57–64.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Khongorzul P, Ling CJ, Khan FU, Ihsan AU, Zhang J. Antibody-drug conjugates: a. Review Mol Cancer Res. 2020;18:3–19.

    Article  CAS  PubMed  Google Scholar 

  56. Baah S, Laws M, Rahman KM. Antibody-drug conjugates-a tutorial review. Molecules. 2021;26:2943.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Gryshkova V, Goncharuk I, Gurtovyy V, Khozhayenko Y, Nespryadko S, Vorobjova L, et al. The study of phosphate transporter NAPI2B expression in different histological types of epithelial ovarian cancer. Exp Oncol. 2009;31:37–42.

    CAS  PubMed  Google Scholar 

  58. Wu B, Yu C, Zhou B, Huang T, Gao L, Liu T, et al. Overexpression of TROP2 promotes proliferation and invasion of ovarian cancer cells. Exp Ther Med. 2017;14:1947–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Thomas LJ, Vitale L, O’Neill T, Dolnick RY, Wallace PK, Minderman H, et al. Development of a novel antibody-drug conjugate for the potential treatment of ovarian, lung, and renal cell carcinoma expressing TIM-1. Mol Cancer Ther. 2016;15:2946–54.

    Article  CAS  PubMed  Google Scholar 

  60. Manzano A, Ocana A. Antibody-drug conjugates: a promising novel therapy for the treatment of ovarian cancer. Cancers (Basel). 2020;12:2223.

    Article  CAS  Google Scholar 

  61. Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, et al. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021;32:757–65.

    Article  CAS  PubMed  Google Scholar 

  62. O’Malley DM, Matulonis UA, Birrer MJ, Castro CM, Gilbert L, Vergote I, et al. Phase Ib study of mirvetuximab soravtansine, a folate receptor alpha (FRalpha)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer. Gynecol Oncol. 2020;157:379–85.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan

    Nozomu Yanaihara, Yasushi Iida, Masataka Takenaka, Ayako Kawabata, Takafumi Kuroda & Aikou Okamoto

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  1. Nozomu Yanaihara
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  2. Yasushi Iida
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  3. Masataka Takenaka
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  4. Ayako Kawabata
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  5. Takafumi Kuroda
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  6. Aikou Okamoto
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Correspondence to Nozomu Yanaihara .

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  1. Department of Gynecology and Obstetrics, Graduate School of Med., Kyoto Univ., Kyoto, Japan

    Masaki Mandai

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Yanaihara, N., Iida, Y., Takenaka, M., Kawabata, A., Kuroda, T., Okamoto, A. (2022). Personalized Treatment in Ovarian Cancer. In: Mandai, M. (eds) Personalization in Gynecologic Oncology. Comprehensive Gynecology and Obstetrics. Springer, Singapore. https://doi.org/10.1007/978-981-19-4711-7_1

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