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Cytoreductive surgery followed by chemotherapy and olaparib maintenance in BRCA 1/2 mutated recurrent ovarian cancer: a retrospective MITO group study
  1. Sabrina Chiara Cecere1,
  2. Lucia Musacchio2,3,
  3. Michele Bartoletti4,5,
  4. Vanda Salutari2,
  5. Laura Arenare6,
  6. Domenica Lorusso2,7,8,
  7. Graziana Ronzino9,
  8. Rossella Lauria10,
  9. Gennaro Cormio11,
  10. Emanuele Naglieri12,
  11. Paolo Scollo13,
  12. Claudia Marchetti2,
  13. Francesco Raspagliesi8,
  14. Stefano Greggi14,
  15. Saverio Cinieri15,
  16. Alice Bergamini16,17,
  17. Michele Orditura18,
  18. Giorgio Valabrega19,20,
  19. Giovanni Scambia2,7,
  20. Fabio Martinelli8,
  21. Elisabetta De Matteis9,
  22. Cinzia Cardalesi10,
  23. Vera Loizzi11,
  24. Giorgia Perniola3,
  25. Claudia Carella12,
  26. Giuseppa Scandurra13,
  27. Gaia Giannone19,20 and
  28. Sandro Pignata1
  1. 1Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy
  2. 2Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
  3. 3Department of Maternal and Child Health and Urological Sciences, Policlinico Umberto I, Sapienza, University of Rome, Rome, Italy
  4. 4Unit of Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano, CRO, Aviano, Italy
  5. 5Department of Medicine, University of Udine, Udine, Italy
  6. 6Clinical Trial Unit, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Campania, Italy
  7. 7Department of Life Science and Public Health, Catholic University of Sacred Heart, Largo Agostino Gemelli, Rome, Italy
  8. 8Gynecologic Oncology Unit, Fondazione Istituto Nazionale Tumori IRCCS, Milan, Italy
  9. 9Medical Oncology Unit, Vito Fazzi Hospital, Lecce, Italy
  10. 10Division of Medical Oncology, Azienda Ospedaliera Universitaria Federico II, Napoli, Campania, Italy
  11. 11Gynecologic Oncology Unit, Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy
  12. 12Gynecologic Oncology Unit, Istituto Oncologico di Bari Giovanni Paolo II, Bari, Italy
  13. 13Medical Oncology Unit, Cannizzaro Hospital, Catania, Italy
  14. 14Gynecologic Oncology, National Cancer Institute, Institute for Hospitalization and Care Scientific Foundation Pascale, Napoli, Campania, Italy
  15. 15Division of Medical Oncology, Ospedale “Senatore Antonio Perrino”, Brindisi, Brindisi, Italy
  16. 16Department of Obstetrics and Gynecology, IRCCS, San Raffaele Hospital, Milan, Italy
  17. 17Università Vita Salute San Raffaele, Milan, Italy
  18. 18Università degli Studi della Campania Luigi Vanvitelli, Napoli, Campania, Italy
  19. 19Candiolo Cancer Institute, FPO- IRCCS, Candiolo (TO), Italy
  20. 20Department of Oncology, University of Turin, Torino, Piemonte, Italy
  1. Correspondence to Professor Sandro Pignata, Gynecological Oncology, National Cancer Institute, Naples, Italy; s.pignata{at}istitutotumori.na.it

Abstract

Introduction The role of cytoreductive surgery in the poly-ADP ribose polymerase inhibitors era is not fully investigated. We evaluated the impact of surgery performed prior to platinum-based chemotherapy followed by olaparib maintenance in platinum-sensitive BRCA-mutated recurrent ovarian cancer.

Methods This retrospective study included platinum-sensitive recurrent ovarian cancer BRCA-mutated patients from 13 Multicenter Italian Trials in Ovarian cancer and gynecological malignancies centers treated between September 2015 and May 2019. The primary outcomes were progression-free survival and overall survival. Data on post-progression treatment was also assessed.

Results Among 209 patients, 72 patients (34.5%) underwent cytoreductive surgery followed by platinum-based chemotherapy and olaparib maintenance, while 137 patients (65.5%) underwent chemotherapy treatment alone. After a median follow-up of 37.3 months (95% CI: 33.4 to 40.8), median progression-free survival in the surgery group was not reached, compared with 11 months in patients receiving chemotherapy alone (P<0.001). Median overall survival was nearly double in patients undergoing surgery before chemotherapy (55 vs 28 months, P<0.001). Post-progression therapy was assessed in 127 patients: response rate to chemotherapy was 29.2%, 8.8%, and 9.0% in patients with platinum-free interval >12 months, between 6 and 12 months, and <6 months, respectively.

Conclusion Cytoreductive surgery performed before platinum therapy and olaparib maintenance was associated with longer progression-free survival and overall survival in BRCA-mutated platinum-sensitive relapsed ovarian cancer patients. In accordance with our preliminary results, the response rate to chemotherapy given after progression during olaparib was associated with platinum-free interval.

  • ovarian cancer
  • cytoreduction surgical procedures

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Footnotes

  • SCC and LM are joint first authors.

  • Twitter @lucia_musacchio, @Barto_Med, @DrFMartinelli, @PignataSandro

  • SCC and LM contributed equally.

  • Contributors Conceptualization SP, SCC; data curation LM, SCC, MB; formal analysis LA, LM; investigation SCC, LM, SP; methodology SCC, LM, SP; project administration SP; supervision SP; writing original draft SCC, LM, SP. All authors acquired data, and revised and approved the final version of the manuscript.

  • Funding SP is recipient of grants from Associazione Italiana per la Ricerca sul Cancro (AIRC). Grants numbers IG-5776, IG-13114, IG-18921.

  • Competing interests VS has been part of advisory boards of GSK, PharmaMar, Roche, MSD, EISAI, Clovis, AstraZeneca. DL reports personal financial interests (advisory roles) with AstraZeneca, Biocad, Clovis Oncology, Genmab, Merck, MSD, Roche, Tesaro-GSK, Amgen, Immunogen, Pharmamar, and institutional financial interests (Study Grants) with AstraZeneca, Clovis Oncology, MSD, Tesaro-GSK, Pharmamar, Roche. Others Global Clinical Lead ENGOT-CX11 Pembrolizumab; Board of Directors, GCIG (Gynecologic Cancer Inter Group). CM reports an advisory role for GSK, Arquer Diagnostic, Pharmamar, Clovis Oncology, and travel grant from Roche. FR reports honoraria from GSK, Pharmamar, Clovis, MSD as sponsors for meetings. GV is an advisor for AstraZeneca, GSK, Amgen, and received speaking honoraria from AstraZeneca, GSK, Roche, Pharmamar. GS reports honoraria from AstraZeneca, MSD, Roche, Clovis, GSK, Pharmamar, Roche (advisory role), and received institutional financial interest (study grants) from AstraZeneca, MSD, GSK, Pharmamar, and he is a member of the board of the National Health Institute. SP reports honoraria from AstraZeneca, MSD, Roche Clovis, GSK Pfizer Pharmamar.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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