Aplidin in patients with advanced dedifferentiated liposarcomas: A French Sarcoma Group Single-Arm Phase II study

Background: Preclinical data have suggested a therapeutic role of JUN pathway activation in dedifferentiated liposarcoma (DDLPS) tumorigenesis. Aplidin^® is a drug inducing apoptosis through a strong, sustained activation of c-Jun NH2-terminal kinase. Methods: This phase II trial included patients with progressive advanced DDLPS. They received Aplidin^® 5 mg/m² days 1-15, 28-day cycle until disease progression or unacceptable toxicity. The primary end point was the 3-month nonprogression rate (PFS3) defined as the proportion of patients with nonprogressive disease at 3 months. A PFS3 of 40% considered as a reasonable objective to claim drug efficacy. Results: Between August 2012 and May 2013, 24 patients were included. Sixteen had received prior chemotherapy. Twenty-two were assessable for efficacy. The PFS3 was 9.1% [95% confidence interval (CI) 1.1-29.2]. Median progression-free and overall survivals were 1.6 months (95% CI 1.4-2.6) and 9.2 months (95% CI 6.6-). The most frequent adverse events of any grade were nausea, fatigue, anorexia, vomiting and diarrhea. Conclusion: Aplidin^® did not meet the primary end point of this trial and do not deserve further investigation in DDLPS.