Clinical activity of immune checkpoint inhibitors in patients with advanced sarcomas: A retrospective single-center experience.

Abstract

e23569 Background: Sarcomas are rare mesenchymal malignancies with poor outcomes in metastatic disease. Efficacy of immune checkpoint inhibitors in sarcomas is inconsistent. We conducted a retrospective cohort study of sarcoma patients treated with ICIs at the University of New Mexico Comprehensive Cancer Center (UNMCCC) to evaluate survival, response, and outcomes. Methods: We retrospectively reviewed patients with histologically confirmed sarcoma treated with ICIs at UNMCCC from 12/2016 to 12/2024. Patient demographics, disease characteristics, molecular profiles, treatment details, and clinical outcomes were collected. Endpoints included real world progression-free survival (rwPFS), overall survival (OS), time on treatment (ToT) and response rate. Results: Fourteen patients with advanced sarcomas received ICIs. The median age at diagnosis was 66.5 years (range: 37-85), and 57% of patients were male. The most common histologic types of sarcomas were: Undifferentiated pleomorphic sarcoma (UPS) 28.5% (n = 4/14), leiomyosarcoma (21.4%, n = 3/14), dedifferentiated liposarcoma (14.2%, n = 2/14), and myxofibrosarcoma (14.2%, n = 2/14). Although 28.6% of patients (n = 4/14) were initially diagnosed with stage I disease, all patients (n = 14/14) were stage IV at time of ICI initiation. Primary tumor sites included soft tissue/extremities (n = 9/14). Most patients (78%, n = 11/14) had previously received chemotherapy and/or targeted treatment (anthracycline 54%, gemcitabine/docetaxel 36%, and TKI 45%) prior to the initiation of ICIs. ICIs included pembrolizumab (n = 9), pembrolizumab-pharmacologic ascorbate (n = 1), nivolumab (n = 2), ipilimumab-nivolumab (n = 1), ipilimumab-nivolumab-cabozantinib (n = 2), pembrolizumab-axitinib (n = 1). The median time from diagnosis-to-ICI initiation was 402 days. The median ToT was 19.5 weeks. Patients with UPS had a longer median ToT of 47 weeks compared with 16 weeks in patients with leiomyosarcoma. UPS also exhibited the longest mrw-PFS, 10 months (1.84-28.3), and 75% of patients (n = 3/4) remaining on treatment at 3 months. In contrast, patients with leiomyosarcoma had a median rw-PFS of 5.3 months (2.79-8.25). Partial responses were observed in 28.5% of patients, while 28.5% achieved stable disease. Progressive disease occurred in 28.5% of patients. Median overall survival from ICI initiation was 34.5 months (95% CI: 18.2-54.1). Conclusions: We observed heterogenous outcomes across histologic subtypes, with signals of durable clinical benefit particularly among patients with UPS. Despite most patients receiving ICIs in the post-chemotherapy setting, disease control was achieved in over half of the cohort, and nearly one-third experienced partial responses, supporting a potential role for ICIs. Immune-related adverse events were common but were not clearly associated with truncated treatment duration.