Eribulin, trabectedin active against pleomorphic liposarcoma

Eribulin and trabectedin show significant antitumour activity in advanced pleomorphic liposarcoma as compared with conventional chemotherapy, according to retrospective data from the Gustave Roussy cancer centre presented at ESMO SARCOMA 2023.

Among 25 patients with advanced disease, response rates were higher with eribulin (four patients; objective response rate [ORR], 25 percent; disease control rate [DCR], 75 percent) and trabectedin (seven patients; ORR, 57 percent; DCR, 86 percent) when used in the first or later lines of therapy than with conventional doxorubicin-based chemotherapy (17 patients; ORR, 5.9 percent; DCR, 47 percent). [ESMO SARCOMA 2023, abstract 48MO]

“Pleomorphic liposarcoma, a rare high-grade subtype of sarcomas, is the less common among liposarcomas,” said lead study author Dr Tarek Assi, a medical oncologist at Gustave Roussy in Villejuif, France.

Right now, the disease is managed based on guidelines for other types of sarcomas, because the need for specific data on pleomorphic liposarcoma from experienced centres has yet to be filled, Assi noted.

“Larger multicentric data collection with better identification of molecular characteristics is needed to optimize the management of this” rare high-grade subtype of sarcoma, he said.

Assi and colleagues’ study included a total 76 patients (mean age 57 years, 53.9 percent women) with pleomorphic liposarcoma treated at Gustave Roussy between 1988 and 2022. Of these, 77.6 percent had localized disease at diagnosis and 97.2 percent had grade 2 or 3 tumours. The most common places for primary cancers were the lower limbs (41.5 percent), the upper limbs (20.8 percent), and the trunk (19.5 percent).

The median local relapse-free survival (RFS) rates were 81.1 percent at 1 year and 50.1 percent at 5 years, while the metastatic RFS rates were 85.4 percent and 64.8 percent, respectively. Multivariate analysis showed age and gender to be prognostic of local recurrence, while only tumour grade predicted distant relapse.

Overall survival in the entire cohort was 95.6 percent at 1 year and 74.9 percent at 5 years. Adjuvant chemotherapy, which was given in 21 patients, emerged as a negative prognostic biomarker for overall survival.

Sarcomas embody the challenges that come with managing rare cancers, given that this family of cancers widely varies by type. Soft tissue sarcoma, for instance, has over 50 distinct subtypes (including liposarcomas), and each subtype presents with its own distinct medical, predictive, and therapeutic features. [BMC Cancer 2018;18:424]

For liposarcomas, surgery is the treatment standard. Initial treatment options outside of clinical trials are doxorubicin, ifosfamide, or their combination—with or without local treatments. In the second-line and subsequent treatments, options comprise ifosfamide, combinations containing gemcitabine, trabectedin, eribulin, and, potentially, pazopanib. Finally, emerging experimental treatment options include MDM2 inhibitors, CDK4/6 inhibitors, immune checkpoint modulators, XPO1 inhibitors, PPARγ agonists, or various combinations thereof. [Oncol Res Treat 2022;45:525-543]