Cabozantinib and temozolomide in unresectable or metastatic soft tissue sarcomas

New data from a phase II trial, recently published on The Lancet Oncology, show a promising clinical benefit on progression-free survival in patients with unresectable or metastatic leiomyosarcoma.

The study was a multicentre, single-arm phase II trial involving 72 patients with unresectable or metastatic uterine and non-uterine leiomyosarcoma (cohort 1) and other soft tissue sarcomas (cohort 2, exploratory), treated with cabozantinib and temozolomide.  After a median follow-up of 18 months, progression-free survival at 12 weeks was reached by 74% of patients in cohort 1; 48% of patients in cohort 1 and 77% in cohort 2 had died due to disease progression at the end of the study. Treatment was tolerable and did not reveal any new safety signals. As authors point out, «This study is the first multicentre prospective trial of cabozantinib and temozolomide in patients with leiomyosarcoma and other soft tissue sarcomas. We show feasibility, safety, and clinical activity of this drug combination across institutions; our findings support dual targeting of VEGF–MET and DNA-damage pathways as a promising strategy in patients with advanced leiomyosarcoma and selected sarcoma subtypes». They also conclude that «This regimen represents a potential oral, outpatient option for patients who have received standard therapies or those unable to tolerate intensive cytotoxic drugs. Future research should prioritise randomised trials and biomarker driven approaches to refine patient selection and confirm benefit».