A phase II trial of dasatinib found that the drug did not produce strong clinical benefit in most types of advanced sarcoma, though it may have activity in undifferentiated pleomorphic sarcoma.
A phase II trial of dasatinib found that the drug did not produce strong clinical benefit in most types of advanced sarcoma. It may, however, have activity specifically in undifferentiated pleomorphic sarcoma.
“The majority of patients with advanced sarcoma rapidly exhaust chemotherapy options, and new effective treatments are needed,” wrote study authors led by Scott M. Schuetze, MD, PhD, of the University of Michigan in Ann Arbor. Earlier work has suggested that the oral tyrosine kinase inhibitor dasatinib may offer some benefit in these patients.
The new trial was a phase II study involving seven separate cohorts of advanced sarcoma patients divided based on type of sarcoma. It enrolled a total of 200 patients, with five of seven cohorts stopping enrollment early due to a lack of clinical benefit. Results were published online ahead of print in Cancer.
Only the undifferentiated pleomorphic sarcoma and leiomyosarcoma cohorts reached their predefined full enrollment totals, with 48 and 49 patients, respectively. Overall, eight undifferentiated pleomorphic sarcoma patients, six leiomyosarcoma patients, and six osteosarcoma patients experienced a clinical benefit, defined as a complete or partial response within 6 months or stable disease of at least 6 months’ duration. The probability that the clinical benefit rate was at least 25% was 0.008 in the undifferentiated pleomorphic sarcoma cohort and 0.10 in the leiomyosarcoma cohort.
The median progression-free survival in the full cohort was 1.9 months; progression-free survival ranged from 0.9 months in the 13 rhabdomyosarcoma patients to 2.2 months in the leiomyosarcoma cohort. Median overall survival was 8.6 months in all patients, and ranged from 3.9 months in the rhabdomyosarcoma cohort to 16.6 months for the 11 liposarcoma patients.
The 2-year survival rate was highest in the undifferentiated pleomorphic sarcoma patients, at 26%; this was followed by 21% for leiomyosarcoma patients, 15% for osteosarcoma patients, and lower rates in the other cohorts.
Most of the 15 patients (73%) who initiated dasatinib at a 100 mg twice-daily dose required a dose reduction due to toxicity, compared with 31% of those who initiated at 70 mg twice daily. There were a total of 127 serious adverse events in 86 patients, and 50 of those adverse events were attributed to the study drug.
“Dasatinib treatment failed to achieve a sufficient level of activity in these groups of patients with high-grade advanced sarcoma to warrant a follow-up clinical trial, without further investigation to elucidate the potential molecular etiology behind the few cases of tumor response and/or prolonged stability, in any of the sarcoma subtypes studied,” the authors concluded.