You are here

Article Text

Article menu

Download PDFPDF

Oral Sessions
06. Ovarian cancer
#765 Efficacy of maintenance with PARPi in advanced ovarian cancer according to the type of BRCA mutation
Free
  1. Claudia Marchetti1,2,
  2. Anna Fagotti1,2,
  3. Robert Fruscio3,
  4. Chiara Cassani4,
  5. Lorena Incorvaia5,
  6. Maria Teresa Perri1,
  7. Carolina Maria Sassu1,
  8. Maria Seca3,
  9. Cristina Angela Camnasio4,
  10. Elena Giudice2,
  11. Angelo Minucci6,
  12. Eloisa Arbustini7,
  13. Laura Vertechy1,
  14. Serena Maria Boccia1,
  15. Vanda Salutari1,2,
  16. Maria Gabriella Ferrandina1,2,
  17. Lucia Musacchio1,
  18. Antonio Russo5,
  19. Giovanni Scambia1,2 and
  20. Domenica Lorusso1,2
  1. 1Dipartimento Scienze della Salute della Donna, del Bambino e di Sanita` Pubblica, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
  2. 2Dipartimento Scienze della Vita e Sanita` Pubblica, Universita` Cattolica del Sacro Cuore, Rome, Italy
  3. 3Università degli Studi di Milano-Bicocca, Milan, Italy
  4. 4Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
  5. 5Discipline Chirurgiche, Oncologiche e Stomatologiche, Università di Palermo, Palermo, Italy
  6. 6Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  7. 7Center for Inherited Cardiovascular Disease, IRCCS, Fondazione Policlinico San Matteo, Pavia, Italy

Abstract

Introduction/Background Currently, little is known about correlations between the type and location of mutations of the BReast CAncer (BRCA) 1/2 genes and response to Poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer (OC). Clinical data from PAOLA1 study suggest that patients with mutations in DNA binding domain (DNA-BD) of BRCA1 are more sensitive to the combination of olaparib/bevacizumab and mutations in the DNA-BD of BRCA2 confer excellent outcomes. No data are available on mutation types and PARPi single agent sensitivity.

Methodology This multicenter, retrospective study involved BRCA1/2 mutated high-grade serous OC patients receiving PARPi as maintenance, after first-line, platinum-based chemotherapy. Clinical and survival data were collected from 4 academic centers. Patients were classified according to the mutation type: frameshift, missense, nonsense and splicing. The primary outcome was progression-free survival (PFS) among the different groups. PFS was also analyzed according to the involved functional domain (FD) of BRCA1 (RING, DNA-BD or BRCA1 C terminus [BRCT]) and BRCA2 (PALB2, RAD51-BD; DNA-BD).

Abstract #765 Figure 1
Abstract #765 Figure 1

PFS according to BRCA mutation type and site.

Results 140 patients treated between 2018–2022 were included. 81(57%) and 60 (43%) harbored BRCA1 and BRCA2 mutations, respectively. Overall, 79 (56%) patients presented frameshift mutation, 17 (12%) missense, 36 (25.5%) nonsense and 8 (5.7%) splicing mutation.After a median follow-up of 20 months, patients harboring a missense mutation had 3-yr PFS of 94%, compared with 73% of those with a frameshift mutation (p=0.05) and 75% of those with a nonsense mutation (p=0.065) (figure 1A).

Ad regarding the FDs, in patients with DNA-BD mutation of BRCA1/2, 3-yr PFS was 91.4%, compared with 88.7% in mutation in the other domains (p=0.64) (figure 1B).

Conclusion In our cohort, missense mutation in the BRCA1/2 genes seems to confer longer PFS than other mutation types. Therefore, mutation type might impact PARPi response. Larger studies are needed to confirm this hypothesis-generating analysis.

Disclosures None

https://doi.org/10.1136/ijgc-2023-ESGO.38

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.