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Thromboembolic events and antithrombotic prophylaxis in advanced ovarian cancer patients treated with bevacizumab: secondary analysis of the phase IV MITO-16A/MaNGO-OV2A trial
  1. Raimondo Di Liello1,
  2. Laura Arenare1,
  3. Francesco Raspagliesi2,
  4. Giovanni Scambia3,
  5. Carmela Pisano4,
  6. Nicoletta Colombo5,
  7. Simona Frezzini6,
  8. Germana Tognon7,
  9. Grazia Artioli8,
  10. Angiolo Gadducci9,
  11. Rossella Lauria10,
  12. Annamaria Ferrero11,
  13. Saverio Cinieri12,
  14. Andrea De Censi13,
  15. Enrico Breda14,
  16. Paolo Scollo15,
  17. Ugo De Giorgi16,
  18. Andrea Alberto Lissoni17,
  19. Dionyssios Katsaros18,
  20. Domenica Lorusso19,
  21. Vanda Salutari3,
  22. Sabrina Chiara Cecere4,
  23. Mariateresa Lapresa19,
  24. Margherita Nardin6,
  25. Giorgio Bogani2,
  26. Mariagrazia Distefano3,
  27. Stefano Greggi20,
  28. Piera Gargiulo1,
  29. Clorinda Schettino1,
  30. Ciro Gallo21,
  31. Gennaro Daniele22,
  32. Daniela Califano23,
  33. Francesco Perrone1,
  34. Sandro Pignata4 and
  35. Maria Carmela Piccirillo1
  1. 1 Unità Sperimentazioni Cliniche, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy
  2. 2 Dipartimento di Chirurgia, SC Chirurgia Ginecologica, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy
  3. 3 Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Ginecologia Oncologica, Fondazione Policlinico Universitario Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
  4. 4 Oncologia Clinica Sperimentale Uro-Ginecologica, Istituto Nazionale Tumori IRCCS Fondazione G Pascale, Napoli, Italy
  5. 5 Istituto Europeo di Oncologia IRCCS, and Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano-Bicocca, Milano, Italy
  6. 6 Oncologia Medica II e Radiologia, Istituto Oncologico Veneto IRCCS, and Università di Padova, Padova, Italy
  7. 7 Divisione di Ostetricia e Ginecologia, ASST Spedali Civili di Brescia, Università di Brescia, Brescia, Italy
  8. 8 Oncologia Medica, ULSS2 Marca Trevigiana, Treviso, Italy
  9. 9 Dipartimento di Medicina Clinica e Sperimentale, UO Ginecologia e Ostetricia, Università di Pisa, Pisa, Italy
  10. 10 Oncologia Medica, Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, Napoli, Italy
  11. 11 Divisione Universitaria di Ginecologia e Ostetricia, AO Ordine Mauriziano, Torino, Italy
  12. 12 Oncologia Medica, Ospedale Senatore Antonio Perrino, Brindisi, Italy
  13. 13 Oncologia Medica, Ospedali Galliera, Genova, Italy
  14. 14 Dipartimento di Oncologia, Ospedale S. Giovanni Calibita Fatebenefratelli, Roma, Italy
  15. 15 UO Ostetricia e Ginecologia, Dipartimento Materno-Infantile, Ospedale Cannizzaro, Catania, Italy
  16. 16 IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy
  17. 17 Ginecologia Chirurgica, Ospedale S. Gerardo, Monza, Italy
  18. 18 AOU Città della Salute, Dipartimento di Scienze Chirurgiche, Ginecologia Oncologica, Ospedale Ostetrico Ginecologico S Anna, Torino, Italy
  19. 19 Divisione di Ginecologia Medica, Istituto Europeo di Oncologia IRCCS, Milano, Italy
  20. 20 SC Ginecologia Oncologica, Istituto Nazionale Tumori IRCCS Fondazione G Pascale, Napoli, Campania, Italy
  21. 21 Dipartimento di Salute Mentale e Fisica e Medicina Preventiva, Università degli Studi della Campania Luigi Vanvitelli, Napoli, Italy
  22. 22 Direzione Scientifica, Fondazione Policlinico Universitario A Gemelli IRCCS, Roma, Italy
  23. 23 Bersagli Molecolari del Microambiente, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy
  1. Correspondence to Dr Maria Carmela Piccirillo, Unità Sperimentazioni Cliniche, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, 80131NA, Italy; m.piccirillo{at}istitutotumori.na.it

Abstract

Introduction The use of routine antithrombotic prophylaxis is not recommended for advanced cancer patients receiving chemotherapy. The effect of bevacizumab-containing therapy on the risk of thromboembolic events remains controversial in ovarian cancer patients. We report on the incidence of thromboembolic events and the prevalence of antithrombotic therapy in patients enrolled in the single arm, phase IV, MITO-16A/MaNGO-OV2A trial.

Methods In this trial, potential prognostic factors for patients with previously untreated ovarian cancer receiving a combination of platinum-based chemotherapy and bevacizumab were explored and the final analysis has already been reported. In this secondary analysis, the occurrence of thromboembolic events and the use of antithrombotic therapy were described according to the clinical characteristics of the patients. The prognostic role of thromboembolic events for progression-free and overall survival were also evaluated.

Results From October 2012 to November 2014, 398 eligible patients were enrolled. 76 patients (19.1%) were receiving some type of anticoagulant or anti-aggregant treatment at baseline. Overall, 24 thromboembolic events were reported (cumulative incidence of 6.0%). The occurrence of thromboembolic events was not associated with baseline patient characteristics and was not modified by the use of antithrombotic prophylaxis (HR 0.60, 95% CI 0.18 to 2.0). Occurrence of thromboembolic events was not associated with progression-free survival (HR 1.34, 95% CI 0.83 to 2.15) or overall survival (HR 0.78, 95% CI 0.37 to 1.61).

Conclusions In our study, a 6.0% rate of thromboembolic events was reported during treatment with bevacizumab plus chemotherapy. Thromboembolic events were not associated with the clinical characteristics of the patients or with the use of antithrombotic prophylaxis, nor did they significantly affect the long-term prognosis.

Trial registration number NCT01706120

  • ovarian cancer
  • venous thromboembolism

Data availability statement

Data are available upon reasonable request. Data of this study will be shared with publication upon reasonable and motivated request to the Principal Investigator of the study (s.pignata{at}istitutotumori.na.it). The following IPD will be available for sharing: baseline characteristics of patients, treatment data, safety data, follow-up data. There will be no time limit for data sharing.

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Data availability statement

Data are available upon reasonable request. Data of this study will be shared with publication upon reasonable and motivated request to the Principal Investigator of the study (s.pignata{at}istitutotumori.na.it). The following IPD will be available for sharing: baseline characteristics of patients, treatment data, safety data, follow-up data. There will be no time limit for data sharing.

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Footnotes

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  • RDL and LA contributed equally.

  • Contributors GD, CG, FP and SP wrote the protocol. RDL, LA, CG, FP, SP and MCP wrote the first draft of the manuscript. LA and CG performed statistical analysis. FR, GS, CP, NC, SF, GT, GA, AG, RL, AF, SC, ADC, EB, PS, UDG, AAL, DK, DL, VS, SCC, EZ, MN, GB, MD, SG, PG, CS, GD, and DC contributed to results interpretation and to the final version of the manuscript.

  • Funding The MITO-16A/MaNGO-OV2A is a multicenter, national, academic trial sponsored by National Cancer Institute of Naples. Roche Italy provided bevacizumab and partial funding for trial activities and for the translational project. AIRC (Associazione Italiana per la Ricerca sul Cancro) supported translational studies with the IG 5776. AIOM (Associazione Italiana di Oncologia Medica) supported biomarker analysis with a grant. Roche, AIRC and AIOM did not play any role in study design, protocol writing, data collection, data analysis and interpretation and manuscript writing. The corresponding author had full access to all of the data and the final responsibility to submit for publication.

  • Competing interests RDL reports personal fees from Astellas, outside the submitted work. FR reports grants from GSK, grants from MSD, grants from Roche, grants from Pharmamar, grants from AstraZeneca, outside the submitted work. NC reports personal fees from Roche, personal fees from Pharmamar, personal fees from AstraZeneca, personal fees from MSD/Merck, personal fees from Clovis Oncology, personal fees from Tesaro, personal fees from GSK, personal fees from Novartis, personal fees from Pfizer, personal fees from Takeda, personal fees from Biocad, personal fees from Immunogen, personal fees from Mersana, personal fees from Eisai, personal fees from Oncxerna, outside the submitted work. SF reports personal fees from Pharmastar, personal fees from GSK, personal fees from Pfizer, personal fees from Novartis, outside the submitted work. DG reports personal fees from Astellas, personal fees from Bayer, personal fees and non-financial support from BMS, personal fees and non-financial support from Ipsen, personal fees and non-financial support from Janssen, personal fees from Merck, personal fees and non-financial support from Pfizer, grants and personal fees from Sanofi, grants from Roche, from AstraZeneca, outside the submitted work. DL reports personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from Clovis, grants, personal fees and non-financial support from GSK, personal fees from Pharmamar, grants and non-financial support from Genmab, grants, personal fees and non-financial support from MSD, non-financial support from Immunogen, non-financial support from Incyte, non-financial support from Roche, from Amgen, outside the submitted work. VS reports personal fees from MSD, personal fees from GSK, personal fees from Tesaro, personal fees from AstraZeneca, personal fees from Roche, personal fees from Eisai, personal fees from Clovis, outside the submitted work. FP reports personal fees from Bayer, personal fees from Ipsen, personal fees from AstraZeneca, personal fees from Bristol Myers Squibb, personal fees from Sandoz, personal fees from Incyte, personal fees from Celgene, personal fees from Pierre Fabre, personal fees from Janssen-Cilag, outside the submitted work. SP reports grants and personal fees from AstraZeneca, grants and personal fees from MSD, grants and personal fees from Roche, personal fees from Pharmamar, personal fees from Clovis, grants and personal fees from Pfizer, outside the submitted work. MCP reports personal fees from Daichii-Sankyo, personal fees from GSK, personal fees from MSD, grants from Roche, grants and personal fees from AstraZeneca, non-financial support from Bayer, outside the submitted work. The other authors do not declare conflicts of interests.

  • 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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