1949P - Pegylated liposomal doxorubicin (PLD) combined with trabectedin as a treatment option in uterine sarcomas

Background

Conventional use of doxorubicin as a single-agent or in combinations with other drugs in the treatment of uterine sarcomas is associated with dose-limiting toxicities. Doxorubicin plus trabectedin was shown to increase progression-free survival (PFS) at the price of higher toxicity. PLD plus trabectedin revealed to be feasible in larger phase 2 and 3 randomised studies in ovarian cancer. We hypothesise that the therapeutic index of trabectedin plus PLD could be superior to the combination with doxorubicin because of a more favourable toxicity profile.

Methods

In this retrospective single-arm study the clinical outcome was analysed in 21 patients with uterine sarcomas treated with PLD 30 mg/m² plus trabectedin 1.1 mg/m² every three weeks between January 2000 and April 2023 at the University Hospital in Innsbruck. Response evaluation was done every 3 cycles and every 3 months during the post-treatment follow-up. Toxicity was evaluated according to the National Cancer Institute-Common Terminology criteria, on a total of 148 administered cycles in 33 patients.

Results

In 66% of patients PLD plus trabectedin was given as first-line treatment, in 19% and 14% as second and third-line treatment, respectively. After 6 months one patient (4.8%) achieved complete remission (CR), four others (19%) showed a partial remission (PR), resulting in an objective response rate (ORR) of 24%. Four patients (19%) showing stable disease (SD), resulting in a clinical benefit rate (= ORR + SD) of 43%; progression was recorded in 12 patients (57%). Median PFS was 6.0 months (SD: ±21 months), while median overall survival was 26 months (SD: ±32 months). A median of 4 (range: 1-11) cycles per patient were given. Regarding ≥ grade 3 toxicity, thrombocytopenia was recorded in 9%, anaemia in 12% and neutropenia in 36% of patients. Febrile neutropenia was present in 7 patients (21%). Haematologic toxicity was the most frequent reason for dose delays (25 events) and dose reductions in eight cases.

Conclusions

Compared to conventional doxorubicin plus trabectedin, the herein investigated combination shows limited but similar anti-tumor efficacy in metastatic uterine sarcomas, but exhibits a more favourable toxicity profile.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.