Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Original article

Vol. 154 No. 4 (2024)

Feasibility and cost-effectiveness of genetic counselling for all patients with newly diagnosed ovarian cancer: a single-centre retrospective study

DOI
https://doi.org/10.57187/s.3386
Cite this as:
Swiss Med Wkly. 2024;154:3386
Published
15.04.2024

Summary

BACKGROUND AND AIMS OF THE STUDY: Due to its importance for treatment and potential prevention in family members, germline testing for BRCA1/2 in patients with newly diagnosed ovarian cancer is decisive and considered a standard of care. Maintenance therapy with poly(ADP-ribose) polymerase (PARP) inhibitors substantially improves progression-free survival in patients with BRCA mutations and homologous recombination-deficient tumours by inducing synthetic lethality. In Switzerland, they are licensed only for these patients. Therefore, it is crucial to test patients early while they are receiving adjuvant chemotherapy. This study aimed to determine whether genetic counselling followed by homologous recombination deficiency testing is feasible for initialising maintenance therapy within eight weeks and cost-effective in daily practice in Switzerland compared to somatic tumour analysis of all patients at diagnosis.

METHODS: This single-centre retrospective study included 44 patients with newly diagnosed high-grade serous ovarian cancer of a Federation of Gynaecology and Obstetrics (FIGO) stage of IIIA-IVB diagnosed between 12/2020 and 12/2022. It collected the outcomes of genetic counselling, germline testing, and somatic Geneva test for homologous recombination deficiency. Delays in initiating maintenance therapy, total testing costs per patient, and progression-free survival were examined to assess feasibility and cost-effectiveness in clinical practice.

RESULTS: Thirty-seven of 44 patients (84%) with newly diagnosed ovarian cancer received counselling, of which 34 (77%) were tested for germline BRCA and other homologous recombination repair gene mutations. Five (15%) BRCA and three (9%) other homologous recombination deficiency mutations were identified. Eleven of the remaining 26 patients (42%) had tumours with somatic homologous recombination deficiency. The mean time to the initiation of maintenance therapy of 5.2 weeks was not longer than in studies for market authorisation (SOLO1, PAOLA, and PRIMA). The mean testing costs per patient were 3880 Swiss Franks (CHF), compared to 5624 CHF if all patients were tested at diagnosis with the myChoice CDx test (p <0.0001).

CONCLUSION: Using genetic counselling to consent patients with newly diagnosed ovarian cancer for germline testing fulfils the international gold standard. Subsequent somatic homologous recombination deficiency analysis complements testing and identifies more patients who will benefit from PARP inhibitor maintenance therapy. Contrary to previous health cost model studies, the procedure does not increase testing costs in the Swiss population and does not delay maintenance therapy. Therefore, all patients should be offered a primary germline analysis. The challenge for the future will be to ensure sufficient resources for prompt genetic counselling and germline testing.

References

  1. González-Martín A, Harter P, Leary A, Lorusso D, Miller RE, Pothuri B, et al.; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Newly diagnosed and relapsed epithelial ovarian cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023 Oct;34(10):833–48. 10.1016/j.annonc.2023.07.011 DOI: https://doi.org/10.1016/j.annonc.2023.07.011
  2. Matulonis U, Herrstedt J, Oza A, Mahner S, Redondo A, Berton D, et al. Long-term safety and secondary efficacy endpoints in the ENGOT-OV16/NOVA phase III trial of niraparib in recurrent ovarian cancer. Gynecol Oncol. 2021;162:S24–5. 10.1016/S0090-8258(21)00693-4 DOI: https://doi.org/10.1016/S0090-8258(21)00693-4
  3. Poveda A, Floquet A, Ledermann JA, Asher R, Penson RT, Oza AM, et al.; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):620–31. 10.1016/S1470-2045(21)00073-5 DOI: https://doi.org/10.1097/OGX.0000000000000962
  4. Konstantinopoulos PA, Ceccaldi R, Shapiro GI, D’Andrea AD. Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer. Cancer Discov. 2015 Nov;5(11):1137–54. 10.1158/2159-8290.CD-15-0714 DOI: https://doi.org/10.1158/2159-8290.CD-15-0714
  5. Morgan RD, Clamp AR, Barnes BM, Timms K, Schlecht H, Yarram-Smith L, et al. Homologous recombination deficiency in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian cancer: a multi-national observational study. Int J Gynecol Cancer. 2023 Aug;33(8):1253–9. 10.1136/ijgc-2022-004211 DOI: https://doi.org/10.1136/ijgc-2022-004211
  6. Christinat Y, Ho L, Clément S, Genestie C, Sehouli J, Martin AG, et al. 2022-RA-567-ESGO The Geneva HRD test: clinical validation on 469 samples from the PAOLA-1 trial. Int J Gynecol Cancer. 2022;32 Suppl 2:A238–9. DOI: https://doi.org/10.1136/ijgc-2022-ESGO.514
  7. Heitz F, Ataseven B, Staniczok C, Denkert C, Rhiem K, Hahnen E, et al. Implementing HRD Testing in Routine Clinical Practice on Patients with Primary High-Grade Advanced Ovarian Cancer. Cancers (Basel). 2023 Jan;15(3):818. 10.3390/cancers15030818 DOI: https://doi.org/10.3390/cancers15030818
  8. Miller RE, Leary A, Scott CL, Serra V, Lord CJ, Bowtell D, et al. ESMO recommendations on predictive biomarker testing for homologous recombination deficiency and PARP inhibitor benefit in ovarian cancer. Ann Oncol. 2020 Dec;31(12):1606–22. 10.1016/j.annonc.2020.08.2102 DOI: https://doi.org/10.1016/j.annonc.2020.08.2102
  9. DiSilvestro P, Banerjee S, Colombo N, Scambia G, Kim BG, Oaknin A, et al.; SOLO1 Investigators. Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: the SOLO1/GOG 3004 Trial. J Clin Oncol. 2023 Jan;41(3):609–17. 10.1200/JCO.22.01549 DOI: https://doi.org/10.1200/JCO.22.01549
  10. González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, et al.; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019 Dec;381(25):2391–402. 10.1056/NEJMoa1910962
  11. Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, et al.; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019 Dec;381(25):2416–28. 10.1056/NEJMoa1911361 DOI: https://doi.org/10.1056/NEJMoa1911361
  12. Ray-Coquard I, Leary A, Pignata S, Cropet C, González-Martín A, Marth C, et al.; PAOLA-1/ENGOT-ov25 investigators. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ann Oncol. 2023 Aug;34(8):681–92. 10.1016/j.annonc.2023.05.005 DOI: https://doi.org/10.1016/j.annonc.2023.05.005
  13. Gonzalez R, Havrilesky LJ, Myers ER, Secord AA, Dottino JA, Berchuck A, et al. Cost-effectiveness analysis comparing “PARP inhibitors-for-all” to the biomarker-directed use of PARP inhibitor maintenance therapy for newly diagnosed advanced stage ovarian cancer. Gynecol Oncol. 2020 Nov;159(2):483–90. 10.1016/j.ygyno.2020.08.003 DOI: https://doi.org/10.1016/j.ygyno.2020.08.003
  14. Penn CA, Wong MS, Walsh CS. Cost-effectiveness of Maintenance Therapy Based on Molecular Classification Following Treatment of Primary Epithelial Ovarian Cancer in the United States. JAMA Netw Open. 2020 Dec;3(12):e2028620. 10.1001/jamanetworkopen.2020.28620 DOI: https://doi.org/10.1001/jamanetworkopen.2020.28620
  15. Sessa C, Balmaña J, Bober SL, Cardoso MJ, Colombo N, Curigliano G, et al.; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Risk reduction and screening of cancer in hereditary breast-ovarian cancer syndromes: ESMO Clinical Practice Guideline. Ann Oncol. 2023 Jan;34(1):33–47. 10.1016/j.annonc.2022.10.004 DOI: https://doi.org/10.1016/j.annonc.2022.10.004
  16. 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. J Clin Oncol. 2020 Apr;38(11):1222–45. 10.1200/JCO.19.02960 DOI: https://doi.org/10.1200/JCO.19.02960
  17. Eoh KJ, Kim HM, Lee JY, Kim S, Kim SW, Kim YT, et al. Mutation landscape of germline and somatic BRCA1/2 in patients with high-grade serous ovarian cancer. BMC Cancer. 2020 Mar;20(1):204. 10.1186/s12885-020-6693-y DOI: https://doi.org/10.1186/s12885-020-6693-y
  18. Stoll S, Unger S, Azzarello-Burri S, Chappuis P, Graffeo R, Pichert G, et al. Update Swiss guideline for counselling and testing for predisposition to breast, ovarian, pancreatic and prostate cancer. Swiss Med Wkly. 2021 Sep;151(3738):w30038. 10.4414/SMW.2021.w30038 DOI: https://doi.org/10.4414/SMW.2021.w30038
  19. Kwon JS, Tinker AV, Santos J, Compton K, Sun S, Schrader KA, et al. Germline Testing and Somatic Tumor Testing for BRCA1/2 Pathogenic Variants in Ovarian Cancer: What Is the Optimal Sequence of Testing? JCO Precis Oncol. 2022 Oct;6(6):e2200033. 10.1200/PO.22.00033 DOI: https://doi.org/10.1200/PO.22.00033
  20. Analysenliste, Krankenpflege-Leistungsverordnung KLV, Anhang 3. In: (EDI) EDdI, editor. Bundesamt für Gesundheit2023.
  21. 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 Dec;379(26):2495–505. 10.1056/NEJMoa1810858 DOI: https://doi.org/10.1056/NEJMoa1810858
  22. Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, et al.; ICON7 Investigators. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec;365(26):2484–96. 10.1056/NEJMoa1103799 DOI: https://doi.org/10.1056/NEJMoa1103799
  23. Witjes VM, Ligtenberg MJ, Vos JR, Braspenning JC, Ausems MG, Mourits MJ, et al. The most efficient and effective BRCA1/2 testing strategy in epithelial ovarian cancer: Tumor-First or Germline-First? Gynecol Oncol. 2023 Jul;174:121–8. 10.1016/j.ygyno.2023.04.029 DOI: https://doi.org/10.1016/j.ygyno.2023.04.029
  24. González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, et al.; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019 Dec;381(25):2391–402. 10.1056/NEJMoa1910962
  25. Elsea D, Fan L, Mihai A, Moustaid FE, Simmons D, Monberg M, et al. Cost-Effectiveness Analysis of Olaparib in Combination with Bevacizumab Compared with Bevacizumab Monotherapy for the First-Line Maintenance Treatment of Homologous Recombination Deficiency-Positive Advanced Ovarian Cancer. PharmacoEconom Open. 2022 Nov;6(6):811–22. 10.1007/s41669-022-00338-2 DOI: https://doi.org/10.1007/s41669-022-00338-2