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Jones RL, Herzog TJ, Patel SR, et al. Cardiac safety of trabectedin monotherapy or in combination with pegylated liposomal doxorubicin in patients with sarcomas and ovarian cancer. Cancer Med. 2021;10(11):3565-3574doi: 10.1002/cam4.3903.
Jones, R. L., Herzog, T. J., Patel, S. R., von Mehren, M., Schuetze, S. M., Van Tine, B. A., Coleman, R. L., Knoblauch, R., Triantos, S., Hu, P., Shalaby, W., McGowan, T., Monk, B. J., & Demetri, G. D. (2021). Cardiac safety of trabectedin monotherapy or in combination with pegylated liposomal doxorubicin in patients with sarcomas and ovarian cancer. Cancer medicine, 10(11), 3565-3574. https://doi.org/10.1002/cam4.3903
Jones, Robin L, et al. "Cardiac safety of trabectedin monotherapy or in combination with pegylated liposomal doxorubicin in patients with sarcomas and ovarian cancer." Cancer medicine vol. 10,11 (2021): 3565-3574. doi: https://doi.org/10.1002/cam4.3903
Jones RL, Herzog TJ, Patel SR, von Mehren M, Schuetze SM, Van Tine BA, Coleman RL, Knoblauch R, Triantos S, Hu P, Shalaby W, McGowan T, Monk BJ, Demetri GD. Cardiac safety of trabectedin monotherapy or in combination with pegylated liposomal doxorubicin in patients with sarcomas and ovarian cancer. Cancer Med. 2021 Jun;10(11):3565-3574. doi: 10.1002/cam4.3903. Epub 2021 May 07. PMID: 33960681; PMCID: PMC8178483.
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Cancer Med. 2021 Jun;10(11):3565-3574. doi: 10.1002/cam4.3903. Epub 2021 May 07.

Cardiac safety of trabectedin monotherapy or in combination with pegylated liposomal doxorubicin in patients with sarcomas and ovarian cancer.

Cancer medicine

Robin L Jones, Thomas J Herzog, Shreyaskumar R Patel, Margaret von Mehren, Scott M Schuetze, Brian A Van Tine, Robert L Coleman, Roland Knoblauch, Spyros Triantos, Peter Hu, Waleed Shalaby, Tracy McGowan, Bradley J Monk, George D Demetri

Affiliations

  1. Sarcoma Unit, Royal Marsden Hospital/Institute of Cancer Research, London, UK.
  2. University of Cincinnati Cancer Center, University of Cincinnati, Cincinnati, OH, USA.
  3. Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  4. Fox Chase Cancer Center, Philadelphia, PA, USA.
  5. Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
  6. Washington University in St. Louis, St. Louis, MO, USA.
  7. US Oncology Research, The Woodlands, TX, USA.
  8. Janssen Research & Development, LLC, Raritan, NJ, USA.
  9. Medical Group Oncology, Janssen Scientific Affairs, LLC, Horsham, PA, USA.
  10. Arizona Oncology (US Oncology Network), University of Arizona College of Medicine, and Creighton University School of Medicine at St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
  11. Sarcoma Center, Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Harvard Medical School and Ludwig Center at Harvard, Boston, MA, USA.

PMID: 33960681 PMCID: PMC8178483 DOI: 10.1002/cam4.3903

Abstract

BACKGROUND: As with other alkylating agents, cardiac dysfunction can occur with trabectedin therapy for advanced soft tissue sarcomas (STS) or recurrent ovarian cancer (ROC) where treatment options for advanced disease are still limited. Cardiac safety for trabectedin monotherapy (T) for STS or in combination with pegylated liposomal doxorubicin (T+PLD) for ROC was evaluated in this retrospective postmarketing regulatory commitment.

METHODS: Patient data for multiple cardiac-related treatment-emergent adverse events (cTEAEs) were evaluated in pooled analyses of ten phase 2 trials, one phase 3 trial in STS (n = 982), and two phase 3 trials in ROC (n = 1231).

RESULTS: Multivariate analyses on pooled trabectedin data revealed that cardiovascular medical history (risk ratio [RR (95% CI)]: 1.90 [1.24-2.91]; p = 0.003) and age ≥65 years (RR [95% CI]: 1.78 [1.12-2.83]; p = 0.014) were associated with increased risk for cTEAEs. Multivariate analyses showed increased risk of experiencing cTEAEs with T+PLD compared to PLD monotherapy (RR [95% CI]: 2.70 [1.75-4.17]; p < 0.0001) and with history of prior cardiac medication (RR [95% CI]: 1.88 [1.16-3.05]; p = 0.010).

CONCLUSIONS: For patients with STS or ROC who still have limited treatment options, trabectedin may be initiated after carefully considering benefit versus risk. Trial Registration (ClinicalTrials.gov): NCT01343277; NCT00113607; NCT01846611.

© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Keywords: anthracycline; cardiac toxicity; chemotherapy; patient outcomes; soft tissue sarcomas

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