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 7.

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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Cardiotoxicity
  • Cardiovascular Diseases / diagnosis
  • Child
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Dacarbazine / administration & dosage
  • Dacarbazine / adverse effects
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Doxorubicin / analogs & derivatives*
  • Female
  • Heart / drug effects*
  • Humans
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / drug therapy
  • Ovarian Neoplasms / drug therapy*
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / adverse effects
  • Product Surveillance, Postmarketing
  • Retrospective Studies
  • Sarcoma / drug therapy*
  • Soft Tissue Neoplasms / drug therapy
  • Stroke Volume / drug effects
  • Trabectedin / administration & dosage
  • Trabectedin / adverse effects*
  • Ventricular Function, Left / drug effects
  • Young Adult

Substances

  • Antineoplastic Agents, Alkylating
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Dacarbazine
  • Doxorubicin
  • Trabectedin

Associated data

  • ClinicalTrials.gov/NCT01846611
  • ClinicalTrials.gov/NCT01343277
  • ClinicalTrials.gov/NCT00113607