(P 110) INTERNATIONAL MULTICENTER RETROSPECTIVE STUDY OF PLEOMORPHIC RHABDOMYOSARCOMA (P-RMS), A PUSH PLATFORM STUDY: OUTCOME OF LOCALIZED AND ADVANCED DISEASE

Objective: Pleomorphic rhabdomyosarcoma (P-RMS) is an ultra-rare sarcoma. Based on available data, 5-year overall survival (OS) ranges between 20% and 40%, while median (m-) OS is < 12 months (mos) in the advanced phase. We report on a retrospective cohort of =/>40 years old patients (pts) with primary and advanced P-RMS collected within the PUSH platform, a global consortium aimed at improving knowledge and favor new treatment development of ultra-rare sarcomas.

Methods: This international, multicenter, retrospective study, conducted within the PUSH platform, included patients aged =/>40 years diagnosed with primary localized, locally advanced, and/or metastatic P-RMS at 30 participating institutions from January 2013 to December 2023. Data retrieved included loco-regional and systemic therapies. Eligible patients had to have a pathologically confirmed diagnosis of P-RMS, requiring desmin immunohistochemical expression and any nuclear expression of myogenin (Myf4) and/or MYOD1, confirmed by sarcoma expert pathologists. Main endpoints included OS, disease-free survival (DFS) and progression-free survival (PFS). Data collection is still ongoing, and final data lock is planned for August 2024. Updated results will be presented at the meeting.

Results: As of May 31, 2024, 119 cases from 13/30 institutions were retrospectively identified; 68/119 were included in the localized disease subgroup analysis (Table 1), while 51/119 in the metastatic subgroup (Table 2).

Localized disease
At a m-FU of 41.1 (IQR: 22.8-76.5) mos, 19/68 (27.9%) patients died and 40/68 (58.8%) recurred. 3-year OS was 65.6% (CI: 53.9%-79.8%); 3-year DFS was 40.2% (CI: 29.6%- 54.6%). LR developed in 9/68 (13%) pts and the 3-year crude cumulative incidence (CCI)-LR was 13% (CI:6%-23%).
DM developed in 33/68 (48.5%) pts and the 3-year CCI-DM was 52% (CI: 39%-64%).
27/68 (39.7%) pts with localized disease were treated with pre-operative radiotherapy (RT) and 28/68 (41%) with pre-operative chemotherapy. Size and administration of RT were significant prognostic factors at multivariable analysis for DFS.

Metastatic disease
At a m-FU of 38.6 (IQR: 10.6-72.8) mos, 35/47 (74.4%) pts progressed and 23/47 (48.9%) died (4 pts lost to follow-up).
Median-PFS from diagnosis of metastatic disease was 6.5 (CI: 5-11.9) mos and m-OS was 20.6 (CI: 16.4-NR) mos, overall.
Anthracycline-based regimens (31 pts): m-FU was 49.7 (IRQ: 18.4-95.3) mos, m-PFS from treatment start was 7.5 (CI: 5-13.7), with an ORR of 58% (17 out of 29 pts evaluable for response). Median-OS was 22.2 (CI: 19.1-NR) mos.
Gemcitabine-based regimens (16 pts): m-FU 18.8 (IRQ: 9.8-38.9) mos, m-PFS from treatment start 3.6 (CI: 2.8-NR) mos, with an ORR of 38% (8 out of 13 pts evaluable for response). Median-OS was 7.8 (CI:6.6-NR) mos.
Pazopanib (5 pts): m-FU 17.5 (IQR: 15.5-NA) mos, m-PFS from treatment start was 1.5 (CI: 1.4-NR), with 1 response out of 2 pts evaluable for response. Median-OS was 7.8 (CI:6.6-NR) mos.

Conclusion: This study represents the largest series of adult pts with P-RMS to date, encompassing both localized and metastatic disease. The prognosis for localized disease remains poor. The m-OS of pts with advanced disease is comparable to the OS of metastatic STS, with patients typically able to receive at least two lines of therapies. Anthracycline-based chemotherapy has shown considerable activity (ORR 58%) and could potentially be used in (neo)-adjuvant settings to improve outcomes. These data will be confirmed in a larger series which will be available at the meeting.