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Breast Cancer

, Volume 26, Issue 6, pp 826–834 | Cite as

Fatal events during clinical trials: an evaluation of deaths during breast cancer studies

  • Jenny FurlanettoEmail author
  • Gunter von Minckwitz
  • Bianca Lederer
  • Volker Möbus
  • Andreas Schneeweiss
  • Jens Huober
  • Peter A. Fasching
  • Bernd Gerber
  • Ingo Bauerfeind
  • Ulrike Nitz
  • Hans-Joachim Lück
  • Claus Hanusch
  • Christoph Thomssen
  • Michael Untch
  • Valentina Nekljudova
  • Keyur Mehta
  • Sibylle Loibl
Original Article
  • 60 Downloads

Abstract

Background

Information on deaths occurring during oncological clinical trials has never been systematically assessed. Here, we examine the incidence of death and the profile of patients who died during randomized clinical breast cancer (BC) trials.

Methods

Information on fatal events during German Breast Group (GBG) led BC trials was prospectively captured. Data were derived from the trial databases and death narratives. All deaths were evaluated for possible causes, underlying conditions, treatment relatedness, time point and rate of autopsies.

Results

From 12/1996 to 01/2017, 23,387 patients were treated within 32 trials. Of those 88 (0.4%) died on therapy within 17 trials. Median age was 64 [range 35–84] years, 63.2% of patients had a body mass index (BMI) ≥ 25 kg/m2; 65.9% 1–3 and 22.7% ≥ 4 comorbidities; 61.4% 1–2 cardiovascular risk factors (CRFs); 26.4% took > 3 drugs; 81.7% had ECOG 0; 50.0% stage III, 76.7% luminal BC. The main causes of death were infection (38.6%; of those, 82.3% sepsis, 17.6% pneumonia), heart failure (14.8%), and pulmonary embolism (13.6%). Fatal events mainly occurred within the first 4 therapy cycles (55.7%), in the investigational arm (66.7%) and under anthracycline–taxane-based chemotherapy (51.1%). A relationship with the treatment was declared in 27.3% of the cases. An autopsy was performed in 13.6% of patients.

Conclusions

Death during study treatment was mainly related to infections, and patients with advanced disease, high BMI, underlying comorbidities, CRFs and concomitant medications. If considered for study participation these patients need careful monitoring due to their higher risk for death on study.

Keywords

Death in clinical trial Cause of death Chemotherapy-related death Serious adverse events Rate of autopsy 

Notes

Acknowledgements

We would like to thank all patients participating in the studies and the study teams of the involved studies.

Author contributions

The data were analyzed by JF and BL. All authors interpreted the data. The first draft of the manuscript was written by JF and BL. The decision to submit the manuscript for publication was made by all the authors. All authors contributed to the review of the manuscript. No persons other than the listed authors contributed to the writing of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no potential conflict of interest related to this work.

Statement of ethics

All patients included in the studies analyzed have provided written informed consent for study participation and data collection. All the analyzed trials were approved by the relevant ethics committees.

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Copyright information

© The Japanese Breast Cancer Society 2019

Authors and Affiliations

  • Jenny Furlanetto
    • 1
    Email author
  • Gunter von Minckwitz
    • 1
  • Bianca Lederer
    • 1
  • Volker Möbus
    • 2
  • Andreas Schneeweiss
    • 3
  • Jens Huober
    • 4
  • Peter A. Fasching
    • 5
  • Bernd Gerber
    • 6
  • Ingo Bauerfeind
    • 7
  • Ulrike Nitz
    • 8
  • Hans-Joachim Lück
    • 9
  • Claus Hanusch
    • 10
  • Christoph Thomssen
    • 11
  • Michael Untch
    • 12
  • Valentina Nekljudova
    • 1
  • Keyur Mehta
    • 1
  • Sibylle Loibl
    • 1
  1. 1.German Breast GroupGBG Forschungs GmbHNeu-IsenburgGermany
  2. 2.Department of Gynecology and ObstetricsKlinikum Frankfurt HöchstFrankfurtGermany
  3. 3.Nationales Centrum für TumorerkrankungenHeidelbergGermany
  4. 4.Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum UlmUlmGermany
  5. 5.Universitätsklinikum ErlangenErlangenGermany
  6. 6.Universitäts-FrauenklinikRostockGermany
  7. 7.Klinikum LandshutMunichGermany
  8. 8.Frauenklinik, Universitätsklinikum DüsseldorfDüsseldorfGermany
  9. 9.Gynäkologisch-Onkologische Praxis HannoverHannoverGermany
  10. 10.Department of GynecologyRotkreuzklinikumMunichGermany
  11. 11.Department of GynecologyMartin-Luther University Halle-WittenbergHalle (Saale)Germany
  12. 12.Department of Gynecology and ObstetricsHelios Klinikum Berlin-BuchBerlinGermany

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