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Efficacy of chemotherapy according to BRCA status in patients with high-grade serous ovarian carcinoma at first platinum-sensitive relapse
  1. Flora Brouillard-Saby1,
  2. Caroline Saint-Martin2,
  3. Isabelle Ray-Coquard3,4,
  4. Laurence Gladieff5,
  5. Christophe Pomel6,
  6. Pierre-Emmanuel Colombo7,
  7. Jean-Marc Classe8,
  8. Marion Chevrier2,
  9. Florence Joly9,
  10. Thibault De la Motte Rouge10,
  11. Anne Floquet11,
  12. Renaud Sabatier12,13,
  13. Emmanuel Barranger14,
  14. Hélène Costaz15,
  15. Eric Leblanc16,
  16. Frédéric Marchal17,
  17. Patricia Pautier18,
  18. Lise Bosquet19 and
  19. Manuel Rodrigues1,20
  1. 1Medical Oncology, Institut Curie, Paris, France
  2. 2Biostatistics, Institut Curie, Paris, France
  3. 3Medical Oncology, Centre Leon Berard, Lyon, France
  4. 4Hesper Lab, Université Claude Bernard Lyon 1, Villeurbanne, France
  5. 5Medical Oncology, Institut Claudius Regaud, Toulouse, France
  6. 6Surgical Oncology, Institut Jean Perrin, Clermont-Ferrand, France
  7. 7Surgical Oncology, Institut régional du Cancer de Montpellier, Montpellier, France
  8. 8Surgical Oncology, Institut de Cancérologie de l'Ouest, Saint Herblain, France
  9. 9Medical Oncology, Centre Francois Baclesse, Caen, France
  10. 10Medical Oncology, Centre Eugène Marquis, Rennes, France
  11. 11Medical Oncology, Institut Bergonié, Bordeaux, France
  12. 12Medical Oncology, Paoli-Calmettes Institute, Marseille, France
  13. 13SESSTIM, Marseille, France
  14. 14Surgical Oncology, Centre Antoine-Lacassagne, Nice, France
  15. 15Surgical Oncology, Centre Georges-François Leclerc, Dijon, France
  16. 16Surgical Oncology, Centre Oscar Lambret, Lille, France
  17. 17Surgical Oncology, Institut de Cancérologie de Lorraine, Vandoeuvre-les-Nancy, Lorraine, France
  18. 18Medical Oncology, Gustave Roussy, Villejuif, France
  19. 19UNICANCER, Paris, France
  20. 20INSERM U830, Institut Curie, Paris, France
  1. Correspondence to Dr Manuel Rodrigues, Institut Curie, Paris, 75005, France; manuel.rodrigues{at}curie.fr

Abstract

Objective Chemotherapy for high-grade serous ovarian cancers in platinum-sensitive relapse includes carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin. According to in vitro data, BRCA mutated patients are sensitive to replicative stress agents but BRCA status is not yet used for the choice of chemotherapy at relapse. Our aim was to assess these doublets according to BRCA status in first platinum-sensitive relapse.

Methods The ESME ovarian cancer database comprises a multicenter retrospective cohort of patients with ovarian cancer treated in French cancer centers between January 2011 and December 2017. Patients with high-grade serous ovarian cancers at first platinum-sensitive relapse who received one of these doublets were included. The objective was to compare progression-free survival of each chemotherapy doublet according to BRCA status.

Results Among the 10 263 patients in the database, 1539 patients had a first platinum-sensitive relapse: 825 BRCA wild type patients (53.6%) and 304 BRCA mutated patients (19.8%) (7 patients had a homologous recombination mutation and BRCA status was unkown for 403 patients). Median progression-free survival was longer in BRCA mutated patients than in BRCA wild type patients when receiving carboplatin/pegylated liposomal doxorubicin without maintenance treatment (15.8 vs 11.8 months; p<0.001). In contrast, we observed no difference in patients treated with carboplatin/paclitaxel (14.6 vs 14.3 months, respectively; p=0.70) or in those treated with carboplatin/gemcitabine (12.0 vs 9.8 months, respectively; p=0.18). In BRCA wild type patients without maintenance, better progression-free survival occurred with carboplatin/paclitaxel (median progression-free survival 14.3 months) than with carboplatin/gemcitabine and carboplatin/pegylated liposomal doxorubicin (9.8 and 11.8 months, respectively; p=0.017). In BRCA mutated patients without maintenance, there was no difference between the three doublets (median progression-free survival of 14.6, 12.0, and 15.8 months with carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin, respectively; p=0.40).

Conclusion While treatment with carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin shows comparable efficacy in BRCA mutated patients, treatment with carboplatin/paclitaxel appears to be more effective than carboplatin/gemcitabine and carboplatin/pegylated liposomal doxorubicin in BRCA wild type patients with high-grade serous ovarian cancers at first platinum-sensitive relapse.

  • Gynecology
  • Ovarian Cancer
  • Neoplasm Recurrence, Local
  • Cystadenocarcinoma, Serous
  • BRCA1 Protein

Data availability statement

Data may be obtained from a third party and are not publicly available.

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Data availability statement

Data may be obtained from a third party and are not publicly available.

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Footnotes

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  • Contributors MR conceptualized the study and is the guarantor of this work. FB-S, CS-M, MC and MR developed its methodology, conducted research investigation and performed data presentation. LB and MR supervised the study. FB-S and MR wrote and edited the first manuscript. All authors reviewed and approved the final manuscript.

  • Funding This work was supported by Unicancer. The ESME ovarian cancer database is supported by an industrial consortium (AstraZeneca and GlaxoSmithKline). Unicancer manages the ESME ovarian cancer database independently. MR was supported by the Interface INSERM program.

  • Competing interests MR received honoraria from AstraZeneca, MSD, GSK, Immunocore and grant support from Bristol-Myers Squibb and Merck. RS received honoraria from GSK, EISAI, and Novartis and declares research grants from AstraZeneca. TD declares advisory boards from Pfizer, AstraZeneca, GSK, Clovis Oncology, Roche, MSD, Mylan, and Tesaro, research grants from Novartis, Pfizer, MSD, abd Seagen and local PI from Roche, AstraZeneca, GSK, MSD, Pfizer, Netris Pharma, and Seagen. The other authors have no conflicts of interest to declare.

  • 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.