Cabozantinib with or without immune checkpoint inhibition in heavily pretreated patients with advanced sarcoma

PURPOSE: The benefit of cabozantinib with or without immune checkpoint inhibition (ICI) in previously heavily treated patients with advanced sarcoma is not clear. EXPERIMENTAL DESIGN: Retrospective study of heavily pretreated advanced sarcoma patients who received cabozantinib with or without ICI. RESULTS: There were 105 eligible patients with thirty-one different histologic subtypes, a median age of 56 years, and 55% were female. 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, 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%. The median PFS and overall survival (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 histologic subtypes, including osteosarcoma, desmoplastic small round cell tumor, synovial sarcoma, and others, had a PFS of more than 12 months. There was no significant difference in PFS or OS between patients treated with cabozantinib only and patients treated with cabozantinib plus ICI. CONCLUSION: In a cohort of heavily pretreated 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 a viable treatment option.