Long‑term survival of a <em>BRCA2</em> mutation carrier following second ovarian cancer relapse using PARPi therapy: A case report

Bredow,Kathrin; Blümcke,Britta; Schneider,Stephanie; Püsken,Michael; Schmutzler,Rita; Rhiem,Kerstin

doi:10.3892/mco.2022.2570

Long‑term survival of a BRCA2 mutation carrier following second ovarian cancer relapse using PARPi therapy: A case report

Authors:
- Kathrin Bredow
- Britta Blümcke
- Stephanie Schneider
- Michael Püsken
- Rita Schmutzler
- Kerstin Rhiem
View Affiliations

Affiliations: Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University of Cologne and University Hospital Cologne, D‑50931 Cologne, Germany, Department of Gynecology and Gynecologic Oncology, Evang. Kliniken Essen Mitte, D-45136 Essen, Germany, Department of Clinical Radiology, University of Cologne, D‑50931 Cologne, Germany
Published online on: July 21, 2022 https://doi.org/10.3892/mco.2022.2570
Article Number: 137
Copyright: © Bredow et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

BRCA1/2 mutation carriers have lifelong increased risks of developing breast and ovarian cancer. Due to the lack of efficient ovarian cancer screening, patients mainly present when the tumors are at an advanced stage, and the long‑term survival is poor. The application of poly(ADP‑ribose) polymerase (PARP) inhibitors (PARPi) has been used in personalized cancer treatment. Specific strategies to improve the outcome of patients are available and mainly include targeting of BRCA1 or BRCA2 mutations. The aim of the present study was to report the case of a 67‑year old BRCA2 mutation carrier, who was enrolled in 2010 in one of the first PARPi studies (ICEBERG2). The patient exhibited second ovarian cancer (OC) relapse following a platinum‑free interval of 5 months. The third‑line treatment with olaparib monotherapy was initiated in January 2011, without prior surgery or chemotherapy, and achieved a persistent response. The patient demonstrated an unprecedented long‑term survival of >9 years under PARPi monotherapy after the second relapse of OC. The data of the present case report support the use of PARPi as a well‑tolerated and effective long‑term treatment, even for patients with unfavourable prognostic characteristics, such as platinum resistance, without immediately preceding optimal cytoreduction. However, further studies are required to provide more insight into the selection of patients for favourable maintenance treatment.

View Figures

View References

1	World Health Organization: https://www.who.int/ionizing_radiation/research/iarc/en/. March, 2020.
2	Kast K, Rhiem K, Wappenschmidt B, Hahnen E, Hauke J, Bluemcke B, Zarghooni V, Herold N, Ditsch N, Kiechle M, et al: Prevalence of BRCA1/2 germline mutations in 21 401 families with breast and ovarian cancer. J Med Genet. 53:465–471. 2016.PubMed/NCBI View Article : Google Scholar
3	Kuchenbaecker KB, Neuhausen SL, Robson M, Barrowdale D, McGuffog L, Mulligan AM, Andrulis IL, Spurdle AB, Schmidt MK, Schmutzler RK, et al: Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res. 16(3416)2014.PubMed/NCBI View Article : Google Scholar
4	Gadducci A and Guerrieri ME: PARP inhibitors alone and in combination with other biological agents in homologous recombination deficient epithelial ovarian cancer: From the basic research to the clinic. Crit Rev Oncol Hematol. 114:153–165. 2017.PubMed/NCBI View Article : Google Scholar
5	Bolton KL, Chenevix-Trench G, Goh C, Sadetzki S, Ramus SJ, Karlan BY, Lambrechts D, Despierre E, Barrowdale D, McGuffog L, et al: Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. JAMA. 307:382–390. 2012.PubMed/NCBI View Article : Google Scholar
6	Chuang YT and Chang CL: Extending platinum-free interval in partially platinum-sensitive recurrent ovarian cancer by a non-platinum regimen: Its possible clinical significance. Taiwan J Obstet Gynecol. 51:336–341. 2012.PubMed/NCBI View Article : Google Scholar
7	Du Bois A, Lück HJ, Meier W, Adams HP, Möbus V, Costa S, Bauknecht T, Richter B, Warm M, Schröder W, et al: A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst. 95:1320–1329. 2003.PubMed/NCBI View Article : Google Scholar
8	Du Bois A, Reuss A, Pujade-Lauraine E, Harter P, Ray-Coquard I and Pfisterer J: Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: A combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: By the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO). Cancer. 115:1234–1244. 2009.PubMed/NCBI View Article : Google Scholar
9	Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, et al: Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 434:917–921. 2005.PubMed/NCBI View Article : Google Scholar
10	Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ and Helleday T: Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 434:913–917. 2005.PubMed/NCBI View Article : Google Scholar
11	Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel JN, Oaknin A, Loman N, et al: Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: A proof-of-concept trial. Lancet. 376:245–251. 2010.PubMed/NCBI View Article : Google Scholar
12	Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, et al: Olaparib maintenance therapy in platinumsensitive relapsed ovarian cancer. N Engl J Med. 366:1382–1392. 2012.
13	Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, 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. 17:1579–1589. 2016.PubMed/NCBI View Article : Google Scholar
14	Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, 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, placebocontrolled, phase 3 trial. Lancet Oncol. 18:1274–1284. 2017.PubMed/NCBI View Article : Google Scholar
15	Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, et al: Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 379:2495–2505. 2018.PubMed/NCBI View Article : Google Scholar
16	Mirza MR, Åvall Lundqvist E, Birrer MJ, dePont Christensen R, Nyvang GB, Malander S, Anttila M, Werner TL, Lund B, Lindahl G, et al: Niraparib maintenance therapy in platinumsensitive, recurrent ovarian Cancer. N Engl J Med. 375:2154–2164. 2016.PubMed/NCBI View Article : Google Scholar
17	Dao F, Schlappe BA, Tseng J, Lester J, Nick AM, Lutgendorf SK, McMeekin S, Coleman RL, Moore KN, Karlan BY, et al: Characteristics of 10-year survivors of high-grade serous ovarian carcinoma. Gynecol Oncol. 141:260–263. 2016.PubMed/NCBI View Article : Google Scholar
18	McLaughlin JR, Rosen B and Moody J: Long-term ovarian cancer survival associated with mutation in BRCA1 or BRCA2. J Natl Cancer Inst. 105:141–148. 2013.PubMed/NCBI View Article : Google Scholar
19	Xu K, Yang S and Zhao Y: Prognostic significance of BRCA mutations in ovarian cancer: An updated systematic review with meta-analysis. Oncotarget. 8:285–302. 2017.PubMed/NCBI View Article : Google Scholar
20	Drew Y, Ledermann J, Hall G, Rea D, Glasspool R, Highley M, Jayson G, Sludden J, Murray J, Jamieson D, et al: Phase 2 multicentre trial investigating intermittent and continuous dosing schedules of the poly(ADP-ribose) polymerase inhibitor rucaparib in germline BRCA mutation carriers with advanced ovarian and breast cancer. Br J Cancer. 114:723–730. 2016.PubMed/NCBI View Article : Google Scholar
21	Markman M, Rothman R, Hakes T, Reichman B, Hoskins W, Rubin S, Jones W, Almadrones L and Lewis JL Jr: Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin. J Clin Oncol. 9:389–393. 1991.PubMed/NCBI View Article : Google Scholar
22	Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, et al: Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: The ICON4/AGO-OVAR-2.2 trial. Lancet. 361:2099–2106. 2003.PubMed/NCBI View Article : Google Scholar
23	Bruchim I, Jarchowsky-Dolberg O and Fishman A: Advanced (>second) line chemotherapy in the treatment of patients with recurrent epithelial ovarian cancer. Eur J Obstet Gynecol Reprod Biol. 166:94–98. 2013.PubMed/NCBI View Article : Google Scholar
24	Friedlander M, Matulonis U, Gourley C, du Bois A, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, et al: Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy. Br J Cancer. 119:1075–1085. 2018.PubMed/NCBI View Article : Google Scholar
25	Alsop K, Fereday S, Meldrum C, deFazio A, Emmanuel C, George J, Dobrovic A, Birrer MJ, Webb PM, Stewart C, et al: BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: A report from the Australian Ovarian Cancer Study Group. J Clin Oncol. 30:2654–2663. 2012.PubMed/NCBI View Article : Google Scholar
26	Harter P, Hauke J, Heitz F, Reuss A, Kommoss S, Marmé F, Heimbach A, Prieske K, Richters L, Burges A, et al: Prevalence of deleterious germline variants in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1). PLoS One. 12(e0186043)2017.PubMed/NCBI View Article : Google Scholar
27	Hauke J, Hahnen E, Schneider S, Reuss A, Richters L, Kommoss S, Heimbach A, Marmé F, Schmidt S, Prieske K, et al: Deleterious somatic variants in 473 consecutive individuals with ovarian cancer: Results of the observational AGO-TR1 study (NCT02222883). J Med Genet. 56:574–580. 2019.PubMed/NCBI View Article : Google Scholar
28	González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, et al: PRIMA/ENGOT-OV26/GOG-3012 investigators. niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 381:2391–2402. 2019.PubMed/NCBI View Article : Google Scholar