(P 470) OFF-LABEL TREATMENT AND ULTRARARE SARCOMAS - SINGLE INSTITUTION REPORT

Objective: Off-label therapies have potential benefit of improving poor outcomes in advanced soft tissue and bone sarcomas with some evidence of activity in ultrarare subtypes.

Methods: Patients with locally advanced or metastatic sarcomas, after exhaustion of standard treatments, were retrospectively analyzed. Data on demographics, disease, treatments, and survival were collected. OS and EFS were calculated, with statistical analysis via log-rank tests. DCR and ORR were assessed.

Results: Seventy-four patients treated from September 2019 to April 2025 met criteria. Off-label therapies included: atezolizumab for 2025 met eligibility criteria. Off-label therapies included: atezolizumab for alveolar ASPS (n=11); ivosidenib and pazopanib for chondrosarcoma (n=11; 2 and 9); imatinib and pembrolizumab for chordoma (n=14; 5 and 9); sirolimus for epithelioid hemangioendothelioma EHE (n=8); cabozantinib for Ewing sarcoma ES (n=11); crizotinib and alectinib for inflammatory myofibroblastic tumor IMT (n=1 and 2); sorafenib for osteosarcoma (n=7); pembrolizumab for sclerosing epithelioid sarcoma SEF (n=2). The cohort was 82% metastatic, median age 43, 53% female. Patients ≤30 years comprised 26%, ≥60 years 27%. Median follow-up was 16.8 months; 81 events (33 deaths). Grade 1–2 adverse events occurred in 23 patients; 4 ended treatment. At analysis, 31% continued O-LT, 57% ended due to progression or death. Patients ≤30 had worse meEFS (5 months) vs ≥60 (21.8; p=0.032). DCR was 61%, ORR 15%, only in ASPS (45%), EHE (13%), ES (18%), IMT (67%), SEF (50%). Patients with ≥4 prior lines had shorter OS (8.2 months) and EFS (3.8) vs 2–3 lines (OS 37.8, EFS 16.2; p=0.0016 and 0.0087). Immunotherapy significantly improved OS and EFS versus kinase inhibitors, with median OS not reached vs 9.2 months, and EFS 23.4 vs 4.6 months (p=0.0043 and 0.0069).

Conclusion: Off-label treatments can improve outcomes in ultrarare sarcoma subtypes: ASPS (atezolizumab), EHE (sirolimus), SEF (pembrolizumab). 3-year survival rates and median EFS surpass historical data. Younger patients show more aggressive disease with shorter EFS. Benefit diminishes after the third line, so O-LT should be considered earlier rather than only as a last therapy.

Summary of analysis - sarcoma type, treatment, results as DCR rates, ORR rates, 3-year OS for sarcoma types from M1/locally advanced diagnosis, median OS and median EFS for off-label treatment for sarcoma types.