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

• Published in: Annals of oncology Vol. 26; no. 7; pp. 1465 - 1470
• Main Authors: Toulmonde, M., Le Cesne, A., Piperno-Neumann, S., Penel, N., Chevreau, C., Duffaud, F., Bellera, C., Italiano, A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2015; Oxford University Press
• Subjects: Aged; Aged, 80 and over; Aplidin; dedifferentiated liposarcoma; Depsipeptides - therapeutic use; Disease Progression; Female; Follow-Up Studies; Humans; JUN; Liposarcoma - drug therapy; Liposarcoma - mortality; Liposarcoma - pathology; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Original; Peptides, Cyclic; plitidepsin; Prognosis; Survival Rate; treatment; treatment; plitidepsin; dedifferentiated liposarcoma; JUN; Aplidin
• ISSN: 0923-7534; 1569-8041; 1569-8041
• DOI: 10.1093/annonc/mdv195

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. 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. 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. Aplidin® did not meet the primary end point of this trial and do not deserve further investigation in DDLPS. NCT01876043.