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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 May 7;10(11) :3565-3574
PMID: 33960681    PMCID: PMC8178483    URL: https://www.ncbi.nlm.nih.gov/pubmed/33960681
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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.
2045-7634 Jones, Robin L Orcid: 0000-0003-4173-3844 Herzog, Thomas J Patel, Shreyaskumar R Orcid: 0000-0002-0026-2348 von Mehren, Margaret Orcid: 0000-0001-6158-890x Schuetze, Scott M Van Tine, Brian A Orcid: 0000-0003-4572-6668 Coleman, Robert L Orcid: 0000-0001-9343-8754 Knoblauch, Roland Triantos, Spyros Hu, Peter Shalaby, Waleed McGowan, Tracy Monk, Bradley J Demetri, George D Janssen Research & Development, LLC/ Dr. Miriam and Sheldon Adelson Medical Research Foundation/ Pan-Mass Challenge/ Journal Article United States Cancer Med. 2021 May 7. doi: 10.1002/cam4.3903.