Real-world outcomes of biomarker-intended pembrolizumab use in soft tissue sarcomas.

Abstract

e23574 Background: Pembrolizumab has a tissue-agnostic FDA indication for metastatic or unresectable solid tumors with high tumor mutational burden (TMB-H; ≥10 mut/Mb) or microsatellite instability–high (MSI-H), after exhausting standard treatment options. This is supported by pan-tumor trials including KEYNOTE-158. However, soft tissue sarcomas (STS) had limited representation in pan-tumor trials. Therefore, the real-world effectiveness of pembrolizumab in biomarker-intended advanced STS remains incompletely characterized. Methods: In January 2026, the TriNetX database (171 global healthcare organizations) was queried to identify patients with STS who received pembrolizumab for this diagnosis. ICD-O-3 codes that corresponded to the histological subtype listed in the NCCN Soft Tissue Sarcoma Guidelines (v1.2026) were used to build the cohort. Undifferentiated sarcoma, pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, angiosarcoma, and alveolar soft part sarcoma were excluded to reduce inclusion of histologies where pembrolizumab may be used outside tissue-agnostic biomarker-induced indications. We extracted demographics, biomarker data, overall survival (OS), and pembrolizumab treatment duration using TriNetX Treatment Pathways. Outcomes were measured from index event (first recorded pembrolizumab administration for STS). Results: A total of 145 patients met initial criteria of selected STS histology and pembrolizumab initiation. Median age was 62 with IQR span of 19. There was a slight female predominance at 57.9%. The most common histologies were leiomyosarcoma (37%), sarcoma, NOS (14%), and lipomatous neoplasms (12%). Prior neoplastic agents were documented in 99 (68%) patients. Common prior treatments included gemcitabine (30%), doxorubicin (27%), and pazopanib (14%). Unfortunately, MSI status was reported only in 7% of the cohort and TMB was not reported. One- and two- year OS were 53.6 and 42.6%, respectively, with median OS of 15.9 months from index. Among the 145 patients, 115 received pembrolizumab without concurrent administration of other antineoplastic agents and also had treatment duration data available. Among patients who received concurrent antineoplastic therapy, doxorubicin, lenvatinib, and cabozantinib were among the most commonly used agents. Median pembrolizumab treatment duration in the 115 patients was 4.1 months. Conclusions: Our findings are broadly consistent with KEYNOTE-158 data, thereby supporting the application of biomarker-intended pembrolizumab use in advanced STS. Limitations of our study include retrospective design, potential confounders, and incomplete biomarker evaluation. Prospective studies are needed to validate outcomes in biomarker-confirmed STS.