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569 The Leuven PARPi benefit test as improved approach for prediction of PARPi benefit in the PAOLA-1/ENGOTov25 trial
  1. Liselore Loverix1,
  2. Ignace Vergote1,
  3. Pieter Busschaert2,
  4. Tom Venken2,
  5. Philipp Harter3,
  6. Els Van Nieuwenhuysen1,
  7. Sandro Pignata4,
  8. Thaïs Baert1,
  9. Antonio Gonzalez-Martin5,
  10. Sileny Han1,
  11. Christian Marth6,
  12. Patrick Neven1,
  13. Nicoletta Colombo7,
  14. Toon Van De Putte1,
  15. Patrick Berteloot1,
  16. Johanna Mäenpäa8,
  17. Isabelle Ray-Coquard9,
  18. Eric Pujade-Lauraine10,
  19. Diether Lambrechts2 and
  20. Toon Van Gorp1
  1. 1University Hospitals Leuven, Leuven, Belgium
  2. 2KU Leuven, Leuven, Belgium
  3. 3Evang. Kliniken Essen-Mitte, Essen, Germany
  4. 4Istituto Nazionale Tumori IRCCS Fondazione Pascale, Milan, Italy
  5. 5Cancer Center Clinica Universidad de Navarra, Madrid, Spain
  6. 6Innsbruck Medical University, Innsbruck, Austria
  7. 7Istituto Europeo Oncologia, Milan, Italy
  8. 8Tampere University, Tampere, Finland
  9. 9Centre Leon Berard Lyon, Lyon, France
  10. 10Arcagy-Gineco, Paris, France


Introduction/Background PAOLA-1/ENGOTov25 trial showed PFS and OS benefit with PARP inhibitor (PARPi) and bevacizumab in maintenance treatment of BRCAm and homologous recombination deficient (HRD+) ovarian cancer. However, current available HRD tests, including our earlier reported Leuven HRD test (EJC,2023;188:131–9), can still be improved. We developed the new ‘Leuven PARPi Benefit Test’ as alternative approach to predict benefit of PARPi, and compared our test with the Myriad myChoice CDxPLUS test (Myriad test) in a training and validation cohort of the PAOLA-1 trial.

Methodology Leuven PARPi Benefit Test is based on genome-wide SNPs of the Leuven HRD test and mutation detection of BRCA1/2 coding exons sequenced with a custom-made capture panel. A random forest-based model to identify patients that benefit most of PARPi was used to define an algorithm combining loss of heterozygosity detection with additional copy-number related features and information on functional domains of BRCA variants. The model was trained on 198 samples and validated on 198 separate samples from PAOLA-1.

Results In the validation cohort, the Leuven PARPi Benefit Test classified 47.5%(94/198) samples as positive compared to 56.6%(112/198) with the Myriad test. At 2 years, PFS of Leuven PARPi Benefit Test positive patients was 78.1% vs 32.1% with olaparib vs placebo, respectively (HR 0.32;95% CI 0.181—0.566). For Myriad HRD test positive patients, this was 69.2% vs 34.4% with olaparib vs placebo, respectively(HR0.40;0.248—0.661). For patients with Leuven PARPi Benefit Test positive/BRCAwt tumours, PFS was 70.8% vs 22.2% at 2y (HR 0.18; 0.068—0.487). This was 53.6% vs 29.4% (HR 0.35;0.173—0.700) for patients with Myriad test positive/BRCAwt tumours. There was no difference in 2yPFS with either a negative Leuven PARPi Benefit Test or a negative Myriad HRD test.

Conclusion Leuven PARPi Benefit Test is an improved approach to detect benefit of PARPi in ovarian cancer patients suggesting a better predictive value compared with the Myriad test.

Disclosures No financial disclosures, patents pending.

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