(P 353) TREATMENT OF ADVANCED EPITHELIOID SARCOMA WITH COMBINATION TAZEMETOSTAT AND PEMBROLIZUMAB

Objective: Epithelioid sarcoma (ES) is an aggressive soft tissue sarcoma accounting for < 1% of soft tissue sarcomas. Tazemetostat, an oral selective inhibitor of EZH2, is a treatment option for advanced ES. Other treatment options include anthracycline-based or other cytotoxic chemotherapy and tyrosine kinase inhibitors with modest clinical benefit. Here we present data from two patients at a single institution treated with tazemetostat in combination with immune checkpoint inhibitor therapy.

Methods: We conducted a retrospective review of two patients with advanced ES treated with combination tazemetostat and pembrolizumab (PD-1 inhibitor) 200 mg every three weeks at our institution.

Results: Patient A, a 38-year-old man, presented with ES of the right hemipelvis, treated with neoadjuvant adriamycin/cisplatin, surgery, and adjuvant radiation (RT). Four years later found to have metastatic disease, treated with gemcitabine/paclitaxel, pazopanib, and targeted RT. On progression, tazemetostat yielded stable disease for 7 months and continued with RT to a right humerus lesion for 24 additional months. At progression, patient was initiated on combination tazemetostat and pembrolizumab with partial response for 27 months. Adverse events were Grade 2 nausea.

Patient B, a 30-year-old man, presented with ES of the left wrist, treated with surgical resection and adjuvant RT. Two years later found to have metastatic disease, treated with vincristine/cyclophosphamide/ifosfamide/etoposide, gemcitabine/docetaxel, pazopanib, and targeted RT. At progression, tazemetostat yielded stable disease for 20 months and continued with RT to bilateral femur lesions for 3 additional months. On progression, combination pembrolizumab was added to tazemetostat yielding stable disease for 10 months and continued with RT to a scalp lesion for an additional 9 months. Pembrolizumab was held at 19 months for Grade 3 autoimmune pancreatitis. The patient has recovered and continues tazemetostat while considering pembrolizumab resumption.

Conclusion: In both cases, pembrolizumab was added to tazemetostat at progression, yielding sustained and durable response for treatment of ES. This demonstrates the potential for combination epigenetic regulation and immunotherapy in sarcoma.