Successful management of metastatic ovarian carcinosarcoma with olaparib plus bevacizumab: a case report

Background: Ovarian carcinosarcoma (OCS) is a rare, highly aggressive, and treatment-resistant tumor. Some important advances in chemotherapy have been reported, including an anti-vascular endothelial growth factor antibody, bevacizumab (Bev)-containing regimen, and a poly-ADP ribose polymerase (PARP) inhibitor, olaparib. Olaparib is specifically a treatment option for OCSs with breast cancer gene (BRCA) mutations, and the clinical study on the combination of olaparib and Bev was reported for homologous recombination deficient epithelial ovarian cancer. However, there are no reports on treating advanced OCS with BRCA mutations by olaparib plus Bev effectively. In this study, to the best of our knowledge, we report the first case of successful management of multiple liver and para-aortic metastases of OCS with a BRCA mutation using olaparib plus Bev. Case: A 75-year-old woman presented to the hospital with complaints of abdominal distension. A staging laparotomy and histological analysis revealed a primary OCS. She received platinum doublet regimens as adjuvant chemotherapy. As myChoice® CDx test of the surgical specimen revealed a BRCA2 mutation, the combination regimen of olaparib (400 mg daily) plus Bev (15 mg/kg every three weeks) was chosen as the maintenance therapy. After four months of this chemotherapy, a computed tomography scan revealed significant shrinkage of both the liver metastases and para-aortic lymph nodes. Progression-free survival has been noted for over 14 months. Conclusions: The combination therapy of olaparib plus Bev could be a potential therapeutic option for advanced OCS.

Ovarian carcinosarcoma; PARP inhibitor; Olaparib; Bevacizumab

[1] Muller M, Dupre P, Lucas B, Simon H, Malhaire J, Guillemet C, et al.[Carcinosarcoma of the ovary]. Journal De Gynecologie, Obstetrique Et Biologie De La Reproduction. 2007; 36: 399–402.

[2] Brown E, Stewart M, Rye T, Al-Nafussi A, Williams ARW, Bradburn M, et al. Carcinosarcoma of the ovary: 19 years of prospective data from a single center. Cancer. 2004; 100: 2148–2153.

[3] Petru E, Kolovetsiou V, Idris T. Prolonged response to trabectedin in a patient with ovarian carcinosarcoma refractory to adjuvant platinum-taxane. Journal. Solid Tumors. 2013; 3: 9–11.

[4] Ray-Coquard IL, Leary A, Bigot F, Montane L, Fabbro M, Hardy-Bessard A, et al. ROCSAN trial (GINECO-EN203b/ENGOT-EN8): a multi-centric randomized phase II/III evaluating dostarlimab in combination with niraparib versus niraparib alone compared to chemotherapy in the treatment of endometrial/ovarian carcinosarcoma after at least one line of platinum based chemotherapy. Journal of Clinical Oncology. 2021; 39: TPS5604–TPS5604.

[5] Koyanagi T, To Y, Ando M, et al. Primary peritoneal carcinosarcoma arising from the Douglas pouch: A case report. Molecular and clinical oncology. 2018; 9: 485–488.

[6] Pennington KP, Walsh T, Harrell MI, Lee MK, Pennil CC, Rendi MH, et al. Germline and Somatic Mutations in Homologous Recombination Genes Predict Platinum Response and Survival in Ovarian, Fallopian Tube, and Peritoneal Carcinomas. Clinical Cancer Research. 2014; 20: 764–775.

[7] Ni J, Zhou R, Cheng X, Xu X, Guo W, Chen X. Tumor burden is a potential marker of PARP inhibitor effects in ovarian cancer: a head-to-head observational series. Journal of Ovarian Research. 2020; 13: 29.

[8] Nagamata S, Nakasuji Y, Yamanaka K, Azumi M, Washio K, Shimizu M, et al. A Case of Significant Response to Olaparib in a Patient with Primary Peritoneal Carcinosarcoma Diagnosed by Laparoscopic Surgery. Case Reports in Obstetrics and Gynecology. 2020; 2020: 9106390.

[9] Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, et al. Olaparib plus Bevacizumab as first-Line Maintenance in Ovarian Cancer. New England Journal of Medicine. 2019; 381: 2416–2428.

[10] Makris GM, Siristatidis C, Battista MJ, Chrelias C. Ovarian carci-nosarcoma: a case report, diagnosis, treatment and literature review. Hippokratia. 2015; 19: 256–259.

[11] Olsen AB, Pargman S, Gillespie T. Solitary splenic metastasis from ovarian carcinosarcoma: a case report. Journal of Medical Case Reports. 2011; 5: 56.

[12] Asano M, Hasegawa K, Tsukada K, Tada S, Mizoguchi Y, Imaeda Y, et al. [A case and literature review of ovarian carcinosarcoma with long-term survival after repeated recurrences]. Gan to Kagaku Ryoho. Cancer & Chemotherapy. 2014; 41: 1031–1036.

[13] Tewari KS, Burger RA, Enserro D, et al. Final overall survival of a randomized trial of bevacizumab for primary treatment of ovarian cancer. Journal of Clinical Oncology. 2019; 37: 2317–2328.

[14] Konstantinopoulos PA, Norquist B, Lacchetti C, Armstrong D, Grisham RN, Goodfellow PJ, et al. Germline and Somatic Tumor Testing in Epithelial Ovarian Cancer: ASCO Guideline. Journal of Clinical Oncology. 2020; 38: 1222–1245.