Aplidin in patients with advanced dedifferentiated liposarcomas: a French Sarcoma Group Single-Arm Phase II study
Mené en France sur 24 patients atteints d'un liposarcome dédifférencié de stade avancé, cet essai de phase II évalue l'efficacité, du point de vue du pourcentage de patients dont la maladie n'a pas progressé après 3 mois de traitement, et la toxicité de l'aplidine
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. ClinicalTrials.gov Identifier : NCT01876043.