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

Abstract

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/m(2) 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.

Clinicaltrialsgov identifier: NCT01876043.

Keywords: Aplidin; JUN; dedifferentiated liposarcoma; plitidepsin; treatment.

© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Figures

Figure 1.

Kaplan-Meier curves of progression-free (A) and overall survivals (B) of patients with advanced DDLPS treated with Aplidin.