Abstract CT004: Safety of prolonged checkpoint inhibitor exposure in alveolar soft part sarcoma (ASPS) patients

Immune checkpoint inhibitors (ICIs) are often stopped after 2 years (yrs) because studies have shown no overall survival benefit beyond 2 yrs and prolonged exposure has the potential to produce late-onset adverse events (AEs). However, questions remain about optimal treatment duration. Data in sarcoma are anecdotal and not confined to a specific histology; clinical trial data are lacking. The efficacy of atezolizumab (atezo) in advanced ASPS was demonstrated in a phase 2 trial, with an objective response rate of 37% reported.1 The trial has further matured and the duration of atezo monotherapy (monoTx) response now ranges from 10 to 69 months. We analyzed the safety data of patients (pts) who received more than 34 cycles (c) (i.e., >2 yrs) of atezo, either as monoTx or with the VEGF inhibitor bevacizumab (NCT03141684). Pts >2 yrs old with unresectable or metastatic ASPS were treated with 1200 mg/m2 atezo or a pediatric dose of 15 mg/kg q 3 weeks. Adult pts whose disease progressed on atezo were given the opportunity to cross over to receive atezo and bevacizumab (15 mg/kg q 3 weeks). Pts were seen q 3 weeks for assessment of AEs, which were reported using CTCAE v5. As of 6/16/25, 54 pts were enrolled. Seventeen pts aged 11-56 years (median: 29) received atezo with or without bevacizumab for >34 c: 12 pts with monoTx only (35-103 c) and 5 pts with monoTx followed by combination therapy (39-124 c across both arms). Three (18%) of the 17 pts reported new onset of grade 2 or 3 treatment-related AEs (TRAEs) after c 34: 1 pt (29 yrs old at entry) experienced grade 3 AST (probable attribution to atezo), 1 pt (31 yrs old at entry) experienced grade 2 hypertension and grade 2 proteinuria (both with a definite attribution to study agents, without distinction between the two), and 1 pt (36 yrs old at entry) experienced grade 2 pruritus (probable attribution to atezo). The pruritus began as grade 1 pruritus during c47; the pt began a drug holiday 2 c later and the pruritus advanced to grade 2 and then resolved with topical and oral medical management 5 months into the holiday. No grade 4 or 5 toxicities were reported. All TRAEs resolved. None of these pts came off study due to toxicity. This is the first report of the safety of prolonged ICI treatment and late AEs in sarcoma, specifically young ASPS pts, with careful monitoring. Late AEs were not seen in this treatment group. This is important in this AYA-dominant sarcoma. With the approval of atezo in multiple countries, real world data will continue to provide insight into the prolonged use of ICs in the young ASPS population. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, and by Genentech Inc. (member of the Roche Group), which provided drug and funding. Reference 1. Chen AP, Sharon E, O'Sullivan-Coyne G, et al. Atezolizumab for Advanced Alveolar Soft Part Sarcoma. New Engl J Med 2023;389:911-921. Citation Format: Alice P. Chen, Nancy Moore, Jared Foster, Christina Rosenberger, Geraldine O'Sullivan Coyne, John Glod, James Hu, Anthony Conley, William Read, Hari Despande, Gary Schwartz, James Chen, Scott Okuno, Richard Riedel, Elad Sharon, James Doroshow. Safety of prolonged checkpoint inhibitor exposure in alveolar soft part sarcoma (ASPS) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT004.