In a phase II study reported in The Lancet Oncology, Monga et al found that dual targeting of vascular endothelial growth factor (VEGF) and mesenchymal epithelial transition factor receptor (MET) pathways with cabozantinib and temozolomide was of benefit in patients with unresectable or metastatic leiomyosarcoma.
Study Details
In the U.S. multicenter study, 72 patients with unresectable or metastatic leiomyosarcoma (cohort 1, n = 42) and other soft-tissue sarcomas (exploratory cohort 2, n = 30) were enrolled between January 2020 and February 2023. Patients received cabozantinib at 40 mg once-daily and temozolomide at 150 mg/m2 on days 1 to 5 of a 28-day cycle for cycle one; starting from cycle two, temozolomide was increased to 200 mg/m2 on days 1 to 5 of each 28-day cycle if the absolute neutrophil count was more than 1.5 × 10⁹/L and the platelet count was more than 100.0 × 10⁹/L. Treatment continued until progression or unacceptable toxicity. The primary outcome measure was progression-free survival at 12 weeks in the leiomyosarcoma cohort.
Key Findings
In the leiomyosarcoma cohort, progression-free survival at 12 weeks was achieved by 31 (74%) of 42 patients who were still receiving cabozantinib and temozolomide; the Kaplan-Meier estimate of progression-free survival at 12 weeks was 79.4% (95% confidence interval [CI] = 68.6%–86.8%), after accounting for censoring and without requiring patients to be receiving treatment at 12 weeks.
Median progression-free survival was 6.3 months (95% CI = 4.6–7.0 months) in the leiomyosarcoma cohort and 3.0 months (95% CI = 1.4–4.6 months) in the exploratory cohort. In post hoc analysis, median overall survival was 19.2 months (95% CI = 11.4 months to not reached) in the leiomyosarcoma cohort and 7.7 months (95% CI = 4.8–10.9 months) in the exploratory cohort; rates at 24 months were 36.4% and 16.8%.
The most common grade 3 to 4 treatment-related adverse events among all patients were platelet count decrease (30%), neutrophil count decrease (18%), hypertension (10%), and diarrhea (8%). No treatment-related deaths were reported.
The investigators concluded: “Cabozantinib with temozolomide showed a meaningful clinical benefit and could potentially be a viable treatment option for patients with unresectable or metastatic leiomyosarcoma. Treatment was tolerable and did not reveal any new safety signals.”
Mark Agulnik, MD, of Division of Medical Oncology, Keck School of Medicine, University of Southern California, Los Angeles, is the corresponding author for The Lancet Oncology article.
DISCLOSURE: The study was funded by Exelixis. For full disclosures of the study authors, visit thelancet.com.
