Survival outcomes of cabozantinib treatment with and without immune checkpoint inhibition in patients with heavily pretreated advanced sarcoma.

11551 Background: Cabozantinib is an oral tyrosine kinase inhibitor (TKI), with key targets including MET, VEGFR2, AXL, RET, and others. It is commonly used to treat specific carcinomas, but its efficacy in treating sarcomas is still emerging, especially in combination with immune checkpoint inhibition. The benefit of cabozantinib with or without immune checkpoint inhibition (ICI) in previously heavily treated patients with advanced sarcoma is unclear, underscoring the need for further investigation. Methods: We report results from a retrospective study of heavily pretreated advanced sarcoma patients who received cabozantinib with or without ICI. Eligible patients included those who had locally advanced or metastatic sarcoma and were exposed to cabozantinib for a minimum of one day. Patients who participated in the clinical trial “Randomized phase II trial of cabozantinib combined with PD-1 and CTLA-4 inhibition versus cabozantinib in metastatic soft tissue sarcoma” were excluded from this study. Results: There were 105 eligible patients with thirty-one different histology types, a median age of 55 years old, of which 55% were female patients. The median lines of prior treatment were four. Approximately 40.9% of patients were treated with cabozantinib alone and 59.1% were treated with cabozantinib plus either nivolumab, or nivolumab plus ipilimumab, or pembrolizumab. The progression-free survival (PFS) of the full cohort was 3.3 months. Eight patients (7.6%) obtained a partial response (PR) and forty-two patients (40.0%) had stable disease (SD) longer than 3 months, with a clinical benefit rate (CBR) of 47.6%. Partial responses occurred across a variety of histologic subtypes, including small round cell tumor, UPS, osteosarcoma, leiomyosarcoma, GIST, liposarcoma, and angiosarcoma. Stable disease was observed in a variety as well, including but not limited to LMS, synovial sarcoma, ASPS, chondrosarcoma, and osteosarcoma. The median PFS and OS for the 47.6% of patients who obtained a clinical benefit (PR + SD) were 6.9 and 22.9 months, compared to the median PFS of 2.1 months (p < 0.001) and median OS of 7.4 months (p = 0.001) for the patients with progressive disease. Several patients with aggressive histology including osteosarcoma, desmoplastic small round cell tumor, synovial sarcoma and others had PFS more than 12 months. Combination therapy with cabozantinib and an ICI accounted for the majority of PR’s observed, including the longest ongoing PR (>15.3 months) in a patient with desmoplastic small round cell tumor. Conclusions: In a cohort of heavily treated patients with advanced soft tissue and bone sarcoma, cabozantinib alone or with ICI showed durable CBR in nearly 50% of patients, suggesting cabozantinib alone or with ICI could be of substantial benefits to certain sarcoma patients who have very limited treatment options remaining.