Current unmet needs in locally advanced (unresectable) or metastatic dedifferentiated liposarcoma, the relevance of progression-free survival as clinical endpoint, and expectations for future clinical trial design: an international Delphi consensus report

• Published in: ESMO open Vol. 9; no. 7; p. 103487
• Main Authors: Schöffski, P., Jones, R.L., Agulnik, M., Blay, J.Y., Chalmers, A., Italiano, A., Pink, D., Stacchiotti, S., Valverde, C., Vincenzi, B., Wagner, M.J., Maki, R.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-07-2024; Elsevier
• Subjects: clinical trial design; Clinical Trials as Topic; Consensus; dedifferentiated liposarcoma; Delphi study; Delphi Technique; Europe; Humans; Liposarcoma - mortality; Liposarcoma - pathology; Liposarcoma - therapy; Progression-Free Survival; Research Design; Review; systemic therapy; unmet need; Europe; clinical trial design; dedifferentiated liposarcoma; Delphi study; systemic therapy; unmet need; progression-free survival
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2024.103487

Locally advanced (unresectable) or metastatic dedifferentiated liposarcoma (DDLPS) is a common presentation of liposarcoma. Despite established diagnostic and treatment guidelines for DDLPS, critical clinical gaps remain driven by diagnostic challenges, symptom burden and the lack of targeted, safe and effective treatments. The objective of this study was to gather expert opinions from Europe and the United States on the management, unmet needs and expectations for clinical trial design as well as the value of progression-free survival (PFS) in this disease. Other aims included raising awareness and educate key stakeholders across healthcare systems.
An international panel of 12 sarcoma key opinion leaders (KOLs) was recruited. The study consisted of two rounds of surveys with pre-defined statements. Experts scored each statement on a 9-point Likert scale. Consensus agreement was defined as ≥75% of experts scoring a statement with ≥7. Revised statements were discussed in a consensus meeting.
Consensus was reached on 43 of 55 pre-defined statements across disease burden, treatment paradigm, unmet needs, value of PFS and its association with overall survival (OS), and cross-over trial design. Twelve statements were deprioritised or merged with other statements. There were no statements where experts disagreed.
This study constitutes the first international Delphi panel on DDLPS. It aimed to explore KOL perception of the disease burden and unmet need in DDLPS, the value of PFS, and its potential translation to OS benefit, as well as the relevance of a cross-over trial design for DDLPS therapies. Results indicate an alignment across Europe and the United States regarding DDLPS management, unmet needs, and expectations for clinical trials. Raising awareness of critical clinical gaps in relation to DDLPS can contribute to improving patient outcomes and supporting the development of innovative treatments.
•DDLPS unmet need is high due to management challenges.•First-line (1L) DDLPS treatments, like doxorubicin, have unsatisfactory efficacy and safety.•PFS is a clinically and patient-relevant primary endpoint in 1L DDPLS.•ORR, DOR, DCP, and PROs are clinically relevant secondary endpoints in 1L DDLPS.•A cross-over clinical trial design is appropriate and well accepted in 1L DDLPS.