Abstract 752P
Background
Epithelioid sarcoma (ES) is a rare subtype of sarcomas. More than 90% of ES have INI1 deletion, which activates EZH2. Preclinical data have proved that INI1 loss leads to genomic instability and a more immunogenic tumor microenvironment, which suggest that immune checkpoint inhibitors may be a promising strategy. However, due to its rarity, there is no compelling evidence for systemic treatment of advanced and metastatic ES.
Methods
We conducted a retrospective study of adults diagnosed as ES at the Zhongshan Hospital, Fudan University from January 2019 to June 2024. The clinical information of the ES patients was collected. RECIST 1.1 and CTCAE 5.0 were used to evaluate the efficacy and safety.
Results
We included 14 advanced or metastatic ES patients, 10 of them were at stage IV. The median age was 38 years (23-57 years); 7 males and 7 females; 4 classic types and 10 proximal types. The first-line treatment included: 1 case with chemotherapy alone, 5 cases with chemotherapy and anti-angiogenesis target therapy, and 8 cases with PD-1 inhibitors combined with chemotherapy and/or target therapies. Chemotherapy mainly included anthracyclines and ifosfamide. Target therapies were anti-angiogenesis TKI anlotinib and EZH2 inhibitor tazemetostat. The median progression-free survival (mPFS) was 3.8 months (95% CI:1.5-NE), and the median overall survival (mOS) was 25.9 months (95% CI:6.5-NE). The PD-1 inhibitor combination therapy had a mPFS of 5.5 months (95% CI:1.5-NE 3.0-NE). The ORR is 27% (2/14) and the DCR is 64% (9/14). The PD-1 inhibitor combination therapy had an ORR of 12.5% (1/8) and DCR of 75% (6/8). One patient treated with PD-1 inhibitors in combination with tazemetostat and anlotinib had a response of PR. The most common grade 3 or higher treatment-related adverse events were neutropenia (2/14), oral mucositis (2/14), anemia (1/14) and fatigue (1/14).
Conclusions
Management of advanced ES remains tricky due to the low efficacy of chemotherapy. Our study provides evidence for the optional regimen in the first-line treatment of ES. The combination strategies with PD-1 inhibitors demonstrated a good anti-tumor response. However, further research is needed to identify patients with ES who may benefit from specific immunotherapy combinations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Zhongshan Hospital Affiliated to Fudan University.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.