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

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ICR Authors

Jones, Robin

Authors

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

Document Type

Journal Article

Date

2020-05-20

Date Accepted

2021-03-03

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.

Citation

Cancer medicine, 2021

DOI

10.1002/cam4.3903

URI

https://repository.icr.ac.uk/handle/internal/4728

Rights

https://creativecommons.org/licenses/by/4.0

Source Title

Publisher

WILEY

ISSN

2045-7634

eISSN

2045-7634

Collections

Clinical Studies

Research Team

Sarcoma Clinical Trials (R Jones)
Sarcoma Clinical Trials (R Jones)

Notes