BRCA screening, treatment patterns and response among patients with

ovarian cancer in the second line treatment setting: results from a real world survey

Objective: Although BRCA gene testing of patients diagnosed with ovarian cancer (OC) is now recommended, the level of testing undertaken in various countries is largely unknown. This study describes BRCA mutation screening patterns and results, demographics, clinical characteristics and the use of poly (ADP-ribose) polymerase inhibitors (PARPi) as maintenance treatment within a real-world sample of patients with advanced OC in the second-line (2L) treatment setting. Methods: Data were collected using the Adelphi Real World OC Disease Specific Programme (DSP)™, a point-in-time survey of physicians and their consulting patients with OC in clinical practice, undertaken across Europe (EU5: France, Germany, Italy, Spain and United Kingdom) and the United States (US) between December 2017–March 2018. Physicians completed a detailed patient record form for their next eight consecutively consulting patients, capturing data on their clinical history and treatment. All analysis was descriptive. Results: Of 1315 patients identified, 1096 (83%) were receiving 2L treatment and 219 (17%) were receiving 2L maintenance treatment; either PARPi (olaparib, rucaparib or niraparib, n = 103) or a non-PARPi (n = 116). BRCA screening rates varied between countries, increased with each line of therapy and were higher in the EU5 (55%) than the US (44%). 28% of patients receiving 2L treatment had a BRCA1/2 mutation. Patients receiving PARPi maintenance treatment had better Eastern Cooperative Oncology Group (ECOG) performance status, higher BRCA screening rates and higher proportions of serous epithelial OC than those receiving 2L treatment or non-PARPi maintenance. Common reasons for choosing 2L treatments were progression-free/overall survival benefit and improvement of quality of life. Conclusions: Despite guidelines recommending BRCA testing in patients with OC, many OC patients undergoing 2L treatment were not screened for BRCA mutations. Decisions related to PARPi use in 2L maintenance appeared to be driven by BRCA status, histology and response to first-line treatment.

BRCA; chemotherapy; second-line; maintenance; ovarian cancer; real-world; PARP inhibitors

[1] Ledermann JA, Raja FA, Fotopoulou C, Gonzalez-Martin A, Colombo N, Sessa C. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2013; 24: vi24–vi32.

[2] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians. 2021; 71: 209–249.

[3] Neff RT, Senter L, Salani R. BRCA mutation in ovarian cancer: testing, implications and treatment considerations. Therapeutic Advances in Medical Oncology. 2017; 9: 519–531.

[4] Ledermann JA, Drew Y, Kristeleit RS. Homologous recombination deficiency and ovarian cancer. European Journal of Cancer. 2016; 60: 49–58.

[5] Colombo N, Sessa C, Bois AD, Ledermann J, McCluggage W, McNeish I, et al. ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. International Journal of Gynecologic Cancer. 2019; 29: 728–760.

[6] National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Epithelial Ovarian Cancer (including Fallopian Tube Cancer and Primary Peritoneal Cancer). 2019. Available at: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1453 (Accessed: 16 December 2021).

[7] Armstrong DK, Alvarez RD, Bakkum-Gamez JN, Barroilhet L, Behbakht K, Berchuck A, et al. NCCN Guidelines Insights: Ovarian Cancer, Version 1.2019. Journal of the National Comprehensive Cancer Network. 2019; 17: 896–909.

[8] Jiang X, Li W, Li X, Bai H, Zhang Z. Current status and future prospects of PARP inhibitor clinical trials in ovarian cancer. Cancer Management and Research. 2019; 11: 4371–4390.

[9] Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. The New England Journal of Medicine. 2016; 375: 2154–2164.

[10] González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, et al. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. New England Journal of Medicine. 2019; 381: 2391–2402.

[11] 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, singlearm, phase 2 trial. The Lancet Oncology. 2019; 20: 636-648.

[12] 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: 1949–1961.

[13] European Society for Medical Oncology. Breakthrough from PAOLA1 GINECO/ENgOT-ov25 trial: Adding Olaparib to Bevacizumab Maintenance Demonstrates Substantial Clinical Benefit in Newly Diagnosed Advanced Ovarian Cancer. Available at: https://www.esmo.org/oncology-news/breakthr ough-from-paola1-gineco-engot-ov25-trial-adding-olaparib-to- bevacizumab-maintenance-demonstrates-substantial-clini cal-benefit-in-newly-diagnosed-advanced-ovarian-cancer#:~: text=Patients%20with%20newly%20diagnosed%20ovarian,p hase%20III\%20study%20findings%20presented (Accessed: 28 September 2019).

[14] 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.

[15] Moore K, Colombo N, Scambia G, Kim B, Oaknin A, Friedlander M, et al. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. The New England Journal of Medicine. 2018; 379: 2495–2505.

[16] 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. The Lancet. Oncology. 2017; 18: 1274–1284.

[17] Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA, Bidziński 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. Journal of Clinical Oncology. 2020; 38: 1164–1174.

[18] Anderson P, Benford M, Harris N, Karavali M, Piercy J. Real-world physician and patient behaviour across countries: Disease-Specific Programmes - a means to understand. Current Medical Research and Opinion. 2008; 24: 3063–3072.

[19] Babineaux SM, Curtis B, Holbrook T, Milligan G, Piercy J. Evidence for validity of a national physician and patient-reported, crosssectional survey in China and UK: the Disease Specific Programme. BMJ Open. 2016; 6: e010352.

[20] Higgins V, Piercy J, Roughley A, Milligan G, Leith A, Siddall J, et al. Trends in medication use in patients with type 2 diabetes mellitus: a long-term view of real-world treatment between 2000 and 2015. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2016; 9: 371–380.

[21] European Pharmaceutical Market Research Associa-tion (EphMRA). Code of Conduct. 2020. Available at: https://www.ephmra.org/media/2811/ephmra-2019-code-of-c onduct-doc-f.pdf (Accessed: 16 December 2021).

[22] US Department of Health and Human Services. Summary of the HIPAA Privacy Rule. 2003. Available at: https://www.hhs.gov/sites/default/files/ocr/privacy/hipaa/un derstanding/summary/privacysummary.pdf (Accessed: 16 December 2021).

[23] Health Information Technology (HITECH). Health Information Technology Act. 2009. Available at: https://crsreports.congress. gov/product/pdf/R/R40161/9 (Accessed: 16 December 2021).

[24] Mavaddat N, Peock S, Frost D, Ellis S, Platte R, Fineberg E, et al. Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. Journal of the National Cancer Institute. 2013; 105: 812–822.

[25] O’Connor MJ. Targeting the DNA Damage Response in Cancer. Molecular Cell. 2015; 60: 547–560.

[26] Girolimetti G, Perrone AM, Santini D, Barbieri E, Guerra F, Ferrari S, et al. BRCA-associated ovarian cancer: from molecular genetics to risk management. BioMed Research International. 2014; 2014: 787143.

[27] Kurian AW, Ward KC, Howlader N, Deapen D, Hamilton AS,

[28] Hoppe MM, Sundar R, Tan DSP, Jeyasekharan AD. Biomarkers for Homologous Recombination Deficiency in Cancer. Journal of the National Cancer Institute. 2018; 110: 704–713.

[29] Pellegrino B, Mateo J, Serra V, Balmaña J. Controversies in oncology: are genomic tests quantifying homologous recombination repair deficiency (HRD) useful for treatment decision making? ESMO Open. 2019; 4: e000480.