The prognosis of relapsed and unresectable high-grade osteosarcoma (OS) and Ewing sarcoma (ES) is dismal and unchanged over the last decades. There are no approved drugs in this setting. Pharmacologic inhibition of Met signaling and of aberrant angiogenesis has shown promising results in in several preclinical models of OS and ES.
These are 2 multicentre single-arm 2-stage phase 2 trials assessing efficacy and safety of cabozantinib in patients (pts) with advanced OS or ES. Pts receive cabozantinib (oral route, adults: 60 mg, children: 40 mg/m²), daily until progressive disease (PD) or unacceptable toxicity. For OS, the primary endpoint is a dual one based on 6-month objective response (OR) and non-progression. Assuming 25% 6-month non-PD (H0), 50% acceptable 6-month non-PD (H1); 5% OR (H0), 20% OR (H1); 5% type I error, 90% power, 41 assessable pts are necessary. The study will be considered as positive if at least 5 patients have OR or 16 patients are progression-free at 6 months. For ES, the primary endpoint is OR. Assuming 5% OR (H0), 20% OR (H1); 5% type I error, 90% power, 41 assessable pts are necessary. The study will be considered as positive if at least 5 patients have OR. Accrual started in 03/2015 in 15 centers of the FSG.
90 pts (45 OS and 45 ES) were included. At the time of statistical analysis, 42 pts with OS and 33 pts with ES were eligible and evaluable for the 1st endpoint after central histological and radiological review. Median age was 34.5 (13–74) and 33 y (13–60) in the OS and ES cohorts respectively. The median number of previous lines of was 3 (1-7) and 4 (1-7) in the OS and ES cohorts respectively. 72 pts (96.0%) had at least one adverse event. 19 OS pts (45.2%) had tumor shrinkage: 5 (11.9%) with partial response (PR) and 14 (33.3%) with stable disease (SD). 19 ES pts (57.6%) had tumor shrinkage: 9 (27.7%) with PR and 10 (30.3%) with SD. 14 OS pts (33.3%) and 8 ES pts (24.2%) were progression-free at 6 months.
Cabozantinib has shown meaningful clinical activity in OS and ES patients with heavily pre-treated advanced disease and reached the primary endpoint of efficacy in both OS and ES cohorts Final efficacy and safety data will be presented at the meeting.
Clinical trial identification