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624 Benefit from maintenance with parp inhibitor in newly diagnosed ovarian cancer according to the mutation type and site
  1. Claudia Marchetti1,2,
  2. Anna Fagotti1,2,
  3. Robert Fruscio3,
  4. Chiara Cassani4,5,
  5. Lorena Incorvaia6,
  6. Maria Teresa Perri1,
  7. Carolina Maria Sassu1,
  8. Maria De Bonis7,
  9. Marta Seca3,
  10. Cristina Angela Camnasio4,5,
  11. Elena Giudice1,
  12. Angelo Minucci7,
  13. Eloisi Arbustini4,5,
  14. Laura Vertechy1,
  15. Serena Maria Boccia1,
  16. Vanda Salutari1,
  17. Maria Gabriella Ferrandina1,2,
  18. Lucia Musacchio1,
  19. Antonio Russo6,
  20. Giovanni Scambia1,2 and
  21. Domenica Lorusso1,2
  1. 1Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
  2. 2Dipartimento Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Rome, Italy
  3. 3Department of Medicine and Surgery, University of Milan – Bicocca, Milan, Italy
  4. 4Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
  5. 5Unit of Obstetrics and Gynecology, IRCCS San Matteo Foundation, Pavia, Italy
  6. 6Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy
  7. 7Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy


Introduction/Background Little is known about correlations between the type and the location of the BRCA1/2 mutations and the magnitude of response to Poly (ADP-ribose) polymerase inhibitors (PARPi) in advanced ovarian cancer (OC), as maintenance.

Methodology This retrospective study enrolled patients with newly diagnosed BRCA-mutated high-grade serous or endometrioid OC who received PARPi maintenance alone after first-line chemotherapy. Progression-free survival (PFS), as the time interval between the last cycle of platinum and the date of subsequent progression or last follow-up, was compared according to the location in the functional domains of BRCA1 [Really Interesting Gene (RING), DNA-binding domain (DBD), or BRCA1 C-terminal domain (BRCT)] and BRCA2 [RAD51-binding domain (RAD51); DBD]. Besides, survival analysis based on the mutation type (frameshift, missense, nonsense and splicing) was performed.

Results 140 patients who underwent PARPi as first-line maintenance were compared with 128 patients who did not receive PARPi in the same setting. Among them, 62.3% harbored BRCA1m and 37.3% BRCA2m. After a median follow-up of 33 months, benefit from maintenance with PARPi was observed irrespective of the location of BRCAm.

Notably, patients with BRCA1m located in the RING and BRCT domains showed the most significant benefit, with 24-month PFS not reached (NR) (PARPi) in both groups, compared with 11 months in No-PARPi -RING arm [Hazard ratio HR8.62 (1.00–74.81)] and 13 months in No-PARPi-BRCT arm [HR7.82 (1.65–37.15)). In BRCA2m patients, 24-month PFS rates were 39.1% (No-PARPi) and 83.2% (PARPi) in cases of mutations in the RAD51[HR 4.13 (1.66–10.29)].

With regard to mutation type, the greatest effect of PARPi was obtained in the missense mutation group, with 24-month PFS NR (PARPi) vs17 months (No-PARPi), respectively [HR 14.25 (1.85–109.71)].

Conclusion First-line maintenance with PARPi in BRCA-mutated OC patients demonstrated PFS benefit, regardless of mutation location and type, particularly in the RING, BRCT (for BRCA1), RAD51 domains (for BRCA2) and missense mutation.

Disclosures None.

Abstract 624 Table 1

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