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#528 Efficacy of subsequent chemotherapy followed by PARP inhibitor maintenance in patients with advanced ovarian cancer in the phase III PAOLA-1/ENGOT-Ov25 trial
  1. Christian Marth1,
  2. Marie-Ange Mouret-Reynier2,
  3. Domenica Lorusso3,
  4. Claire Cropet4,
  5. Philipp Harter5,
  6. Eva Guerra6,
  7. Takashi Matsumoto7,
  8. Ignace Vergote8,
  9. Nicoletta Colombo9,
  10. Johanna Mäenpää10,
  11. Coriolan Lebreton11,
  12. Nikolaus De Gregorio12,13,
  13. Anna Maria Mosconi14,
  14. María Jesús Rubio15,
  15. Hugues Bourgeois16,
  16. Peter A Fasching17,
  17. Anne-Claire Hardy-Bessard18,
  18. Dominik Denschlag19,
  19. Eric Pujade-Lauraine20 and
  20. Isabelle Ray-Coquard4
  1. 1Department of Obstetrics and Gynaecology, Medical University of Innsbruck, and AGO-Austria, Innsbruck, Austria
  2. 2Centre Jean Perrin, and GINECO, Clermont-Ferrand, France
  3. 3Istituto Tumori Milano + Fondazione Policlinico Universitario A. Gemelli IRCCS and Catholic University of Sacred Heart, and MITO, Rome, Italy
  4. 4Centre Léon BERARD, and GINECO, Lyon, France
  5. 5Kliniken Essen-Mitte, and AGO, Essen, Germany
  6. 6Hospital Universitario Ramón y Cajal, and GEICO, Madrid, Spain
  7. 7Ehime University Hospital, and GOTIC, Toon, Japan
  8. 8University Hospital Leuven, Leuven Cancer Institute, and BGOG, Leuven, Belgium
  9. 9University of Milan-Bicocca and European Institute of Oncology IRCCS, and MANGO, Milan, Italy
  10. 10Tampere University Hospital, and NSGO, Tampere, Finland
  11. 11Institut Bergonié, and GINECO, Bordeaux, France
  12. 12Universitätsklinikum Ulm, Klinik für Frauenheilkunde und Geburtshilfe, and AGO, Ulm, Germany
  13. 13SLK-Kliniken Heilbronn GmbH, Frauenklinik, and AGO, Heilbronn, Germany
  14. 14S.C. di Oncologia Medica Osp. S. Maria della Misericordia – AO di Perugia, and MITO, Perugia, Italy
  15. 15Hospital Reina Sofia, and GEICO, Cordoba, Spain
  16. 16Centre Jean Bernard – Clinique Victor Hugo, and GINECO, Le Mans, France
  17. 17Universitätsfrauenklinik Erlangen, and AGO, Erlangen, Germany
  18. 18Centre CARIO – HPCA, and GINECO, Plérin Sur Mer, France
  19. 19Hochtaunuskliniken, and AGO, Bad Homburg, Germany
  20. 20ARCAGY Research, and GINECO, Paris, France


Introduction/Background In PAOLA-1/ENGOT-ov25 (NCT02477644), maintenance PARP inhibitor (PARPi) olaparib+bevacizumab improved progression-free survival (PFS) in patients with homologous recombination-deficient (HRD+) advanced ovarian cancer (Ray-Coquard. NEJM 2019;381:2416–28). Post-hoc analysis showed the efficacy of subsequent chemotherapy at relapse was reduced in patients who progressed during versus after olaparib treatment (Harter. Presented at ASCO 2023).

In the OReO/ENGOT-ov38 trial (NCT03106987), olaparib rechallenge conferred a modest but statistically significant PFS benefit in patients with platinum-sensitive ovarian cancer (Pujade-Lauraine. Ann Oncol 2021;32:S1308–9), the majority of whom had received initial PARPi therapy in the relapsed setting and, therefore, were most likely to have progressed under PARPi maintenance. We explored PARPi rechallenge in patients who received platinum-based combination therapy (PBC) followed by PARPi (PBC>PARPi) as first subsequent therapy (FST) after progression on first-line treatment in PAOLA-1.

Methodology To explore the efficacy of PBC>PARPi, median time from FST to second subsequent therapy (SST) was analysed post-hoc by timing of progression (during/after olaparib) and tumour HRD status.

Results 544 patients progressed and received subsequent chemotherapy. Time from FST to SST was longer in patients receiving PBC>PARPi (n=159) as FST than in patients receiving PBC without PARPi maintenance (n=293) and was shortest in patients who progressed during olaparib (table 1).

Myelodysplastic syndrome, acute myeloid leukaemia or aplastic anaemia occurred in 3/82 (3.7%) patients in the control arm and no patients who received olaparib. No unexpected toxicity was observed.

Conclusion In this post-hoc exploratory analysis of PAOLA-1, subsequent PBC>PARPi rechallenge led to better outcomes than PBC alone in patients who received olaparib+bevacizumab. Efficacy appeared to depend on whether progression occurred during or after olaparib treatment. Results build on observations from OReO that PARPi rechallenge could be considered for patients responding to PBC, but are limited by small patient numbers and loss of randomisation, and need to be confirmed in a larger randomised study.

Abstract #528 Table 1

Time from FST to SST, months (median)

Disclosures This work was supported by ARCAGY Research, AstraZeneca, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and F. Hoffmann-La Roche.

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