Checkpoint inhibitor and multireceptor tyrosine kinase inhibitor combination in relapsed refractory sarcomas: A single institution series.

11529 Background: Adolescent and young adults (AYA) with primary metastatic and relapsed bone and soft tissue sarcomas (BST) have poor prognosis with progression free survival (PFS) rates < 15% and overall survival (OS) < 20%. These outcomes have not improved in the past three decades, highlighting the need for new treatment paradigms. Immunotherapy is effective for multiple malignancies via blockade of CTLA4 or PD-L1 by immune checkpoint inhibitors (CPI), like nivolumab (NIVO). Sarcomas often express PD-L1 as part of their complex pathogenic pathway. Additionally, combination with oral targeted therapies is an emerging strategy for adult malignancies. Encouraging early phase results with multi-tyrosine kinase inhibitors (TKI) of several pathogenic sarcoma pathways – including lenvatinib (LEN), cabozantinib (CABO), and pazopanib – have prompted our team to offer CPI in combination with a TKI for BST patients without chemotherapy options. Methods: Retrospectively identified AYA patients with relapsed heavily pre-treated BST who received CPI/TKI combination at our institution between January 2018 to date. Results: This is the first reported series of prolonged survival in metastatic and multiply relapsed BST with CPI and TKI therapy. Table summarizes the demographics, disease features, and survival for all patients. The regimen was well tolerated in all patients, except for a rash (n = 1) that resolved by reducing the CABO dose by 25%. All patients had previously been offered palliative care before this regimen. Conclusions: Our preliminary experience with CPI/TKI combination in multiply relapsed BST shows a PFS exceeding prior PFS periods with other therapies for all patients. The overall survival is more than historical controls for initial metastatic ASPS, initial metastatic EWS, and recurrent metastatic OST. Our report will inform colleagues about the potential of CPI/TKI combination for these patients with few options. [Table: see text]