(P 189) INTERNATIONAL RETROSPECTIVE STUDY FROM THE ULTRA-RARE SARCOMA WORKING GROUP ON LOW-GRADE FIBROMYXOID SARCOMA AND SCLEROSING EPITHELIOD FIBROSARCOMA: OUTCOME OF ADVANCED DISEASE AND SYSTEMIC THERAPIES

Objective: To report on the outcome of pts with metastatic low-grade fibromyxoid sarcoma (F) and sclerosing epitheliod sarcoma (S).

Methods: We conducted an international retrospective multicentre study of all consecutive patients (pts) affected by metastatic F and S, observed and treated at the participating institutions of the Utra-Rare Sarcoma Working Group.
Eligible pts had a pathologic diagnosis of F, S or hybrid F/S (requiring strong MUC4 expression and/or the presence of one of the following: FUS/EWSR1 rearrangement, EWSR1/FUS::CREB3L1/CREB3L2/CREM, YAP1::KMT2A). Hybrid F/S were included in the S group. Primary end-point was progression-free survival (PFS), defined as the time from diagnosis of distant metastases until first progression or death, whichever occurred first. Secondary end-points were overall response rate (ORR), and post-metastasis overall survival (OS), defined as the time from the onset of the first distant metastasis and death or last follow-up (FU). PFS and OS were estimated with the Kaplan-Meier method, overall and for the two F and S groups.
A propensity score (PS) matching analysis (variables: age, sex, histology, stage at diagnosis, primary site, surgery) of pts treated vs not treated with first-line was done and weighted Cox models for OS and PFS were fitted to estimate the treatment effect.
The analysis presented herein was performed on cases entered in the database by June 10th 2023; data collection is still ongoing (closure planned by August 31st 2023) and the updated analysis will be presented at the meeting.

Results: 303 eligible pts were identified, 86/303 (28.4%) were metastatic (25 F, 61 S) and are the subject of this analysis (Table 1). 18 F and 49 S pts received at least one line of systemic therapy (Rx) (Table 2).
At a 62.14-mo m-FU (IQR:31.1-82.5), m-OS was: overall = 58.4 (IQR:32.4-NA) mos, F = not reached (IQR:32.4-NA), S = 58.4 (IQR:30.5-83.2) mos; m-PFS was: overall = 23.3 (IQR:9.0-56.4) mos, F = 24.5 (IQR:14.3-67.5) mos, S = 20.3 (IQR:8.8-56.4) mos. Median time to DM was: overall = 29 (IQR:16.7-85.7) mos, F = 79.2 (IQR:62.9-82.3) mos, S = 18 (IQR:17.3-98.8) mos.

In the anthracycline-based Rx group, 1/12 response (PR) was seen in F (ORR 7.1%), 0/29 in S. At 58.9-mo m-FU (IQR:22.6-69.01), m-OS and m-PFS were: overall = 30.5 (IQR:16.4-51.0) and 5.1 (IQR:2.0-20.1) mos, F = 30.6 (IQR:12.6-NA) and 2.6 (IQR:2.0-12.6) mos, S = 29.9 (IQR:23.9-51.0) and 6.8 (IQR:2.0-23.9) mos.
In the gemcitabine-based Rx group, 1/7 PR was seen in F (ORR 14.3%), 0/17 in S. At 81.7-mo m-FU (IQR:31.9-118.0), m-OS and m-PFS were: overall = 69.3 (IQR:32.4-NA) and 29.2 (IQR:8.1-60.3) mos, F = NA (IQR:NA-NA) and 32.4 (IQR:17.3-81.3) mos, S = 48.9 (IQR:30.5-80.1) and 24.2 (IQR:7.5-60.3) mos.
In the pazopanib group, 2/6 PR were seen in F (ORR 28.6%), 1/19 in S (ORR 4.3%). At 36.5-mo m-FU (IQR:13.7-66.2), m-OS and m-PFS were: overall = 29.3 (IQR:13.4-NA) and 10.7 (IQR:2.8-19.5) mos, F = NA (IQR:13.4-NA) and 13.4 (IQR:2.0-19.5) mos, S = 24.4 (IQR:12.0-NA) and 10.6 (IQR:2.8-18.1) mos.
No responses were seen to trabectedin. At 39.7-mo m-FU (IQR:19.6-43.4), m-OS and m-PFS were: overall = 15.0 (IQR:8.4-41.3) and 3.3 (IQR:2.0-7.4) mos, F = NA (IQR:8.4-NA) and 6.2 (IQR:2.3-11.0) mos, S = 14.5 (IQR:8.3-20.5) and 2.1 (IQR:1.9-6.2) mos.
In the “other” Rx group, activity was seen to ifosfamide and oral cyclophosphamide.

The comparison of treated vs not treated pts with first line Rx did not result in a statistically significant difference in PS-adjusted PFS (HR 0.88, 95%CI 0.4-1.94, p-value: 0.759).

Conclusion: The metastatic course of F and S may be indolent. When systemic therapy is needed, gemcitabine-based regimen and pazopanib currently seem to be most active. Responses were seen also to ifosfamide and oral cyclophosphamide. New, effective systemic agents are needed.