Multicenter phase 2 trial of cabozantinib plus temozolomide for unresectable or metastatic leiomyosarcoma and other soft tissue sarcomas

Patients with unresectable or metastatic soft tissue sarcomas (STS) have a poor prognosis. A phase 2 trial at five centers in the USA evaluated dual targeting of VEGF and MET pathways with cabozantinib and temozolomide in patients with unresectable or metastatic leiomyosaroma (LMS) or other STS. The study enrolled 72 adult patients with LMS (cohort 1; n=42) or other STS (exploratory cohort 2; n=30), an ECOG performance status 0 or 1, up to five previous chemotherapy regimens, and adequate organ and bone marrow function. The primary endpoint was progression-free survival at 12 weeks (PFS12) in cohort 1. The median follow-up was 18.0 months (IQR 17.5-20.7). PFS12 was reached by 31 (74%) of 42 patients still receiving treatment. The Kaplan-Meier estimate of PFS was higher due to censoring and not requiring patients to be receiving treatment at 12 weeks (79%; 95% CI 68.6-86.8). Twenty patients in cohort 1 (48%) and 23 patients in cohort 2 (77%) had died due to disease progression at the end of the study. Treatment-related adverse events were reported for 71 of 72 patients (99%). There were no treatment-related deaths. The authors conclude that cabozantinib plus temozolomide showed a meaningful clinical benefit among patients with unresectable or metastatic LMS.