A Phase 1 Study of Neoadjuvant Cabozantinib in Combination With Radiation Therapy for Sarcomas of the Extremities.
Hannah R Abrams, Elizabeth T Loggers, Michael J Wagner et al.
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In 30 seconds
This phase 1 trial evaluated the safety and dose of neoadjuvant cabozantinib given concurrently with radiation therapy before surgery in adults with newly diagnosed, localized extremity soft tissue sarcoma. Six patients with several sarcoma subtypes received radiation and cabozantinib. No dose-limiting toxicity from the combination was observed, and the recommended phase 2 dose was cabozantinib 60 mg. However, 3/6 (50%) patients required cabozantinib dose reduction for treatment-related adverse events attributed to cabozantinib alone. The authors concluded that concurrent treatment was feasible with an acceptable safety profile.
Key findings
- No dose-limiting toxicity due to concurrent cabozantinib and radiation was observed among six patients.
- The recommended phase 2 dose was cabozantinib 60 mg; 3/6 (50%) patients required dose reduction for cabozantinib-related adverse events.
- All six patients had stable disease at 12 weeks, and 5 (83%) underwent R0 resection.
- No local recurrences occurred; 2 (33%) patients had metastatic relapse and 1 (17%) died without relapse.
Why it matters
Concurrent targeted therapy and radiation can raise concern about serious tissue complications. This small phase 1 study provides preliminary safety and dosing information for combining cabozantinib with neoadjuvant radiation in extremity sarcoma, while the frequent dose reductions underscore the need to consider cabozantinib-related toxicity. The findings are early and do not establish comparative efficacy.
What to keep in mind
Only six patients were enrolled, limiting the precision and generalisability of safety and outcome estimates.