GDC-0449 in patients with advanced chondrosarcomas: a French Sarcoma Group/US and French National Cancer Institute Single-Arm Phase II Collaborative Study

Pre-clinical data have suggested a therapeutic role of Hedgehog (Hh) pathway inhibitors in chondrosarcoma. This phase II trial included patients with progressive advanced chondrosarcoma. They received GDC-0449 150 mg/day (days 1-28, 28-day cycle). The primary end point was the 6-month clinical benefit rate (CBR) defined as the proportion of patients with non-progressive disease at 6 months. A 6-month CBR of 40% was considered as a reasonable objective to claim drug efficacy. Between February 2011 and February 2012, 45 patients were included. Twenty had received prior chemotherapy. Thirty-nine were assessable for efficacy. The 6-month CBR was 25.6% (95% confidence interval 13.0-42.1). All stable patients had grade 1 or 2 conventional chondrosarcoma with documented progression within the 6 months before inclusion. All but one with available data also had overexpression of the Hh ligand. Median progression-free and overall survivals were 3.5 and 12.4 months, respectively. The most frequent adverse events were grade 1 or 2 myalgia, dysgeusia and alopecia. GDC-0449 did not meet the primary end point of this trial. Results suggest some activity in a subset of patients with progressive grade 1 or 2 conventional chondrosarcoma. Further studies assessing its role in combination with chemotherapy are warranted. NCT01267955.