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

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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Pages (from-to)3565-3574
Number of pages10
JournalCancer medicine
Volume10
Issue number11
DOIs
StatePublished - Jun 2021

Keywords

  • anthracycline
  • cardiac toxicity
  • chemotherapy
  • patient outcomes
  • soft tissue sarcomas

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