(P 135) UNMET NEEDS IN LOCALLY ADVANCED (UNRESECTABLE) OR METASTATIC DEDIFFERENTIATED LIPOSARCOMA AND EXPECTATIONS FOR CLINICAL TRIALS: AN INTERNATIONAL DELPHI CONSENSUS STUDY

Objective: Locally advanced (unresectable) or metastatic dedifferentiated liposarcoma (DDLPS) is a common subtype of liposarcoma. It is often high-grade and aggressive and most often occurs in the retroperitoneum and deep soft tissue of proximal extremities. Anthracycline-based therapy, such as doxorubicin, is considered the standard of care in first line (1L) treatment of DDLPS, either used as a single agent or in combination with an alkylating agent. The objective of this study was to gather expert opinions across Europe and the US on DDLPS management and unmet needs, Progression Free Survival (PFS) relevance as a clinical trial endpoint and expectations for clinical trial design. The study also aimed at building robust evidence on key clinical topics to raise awareness among the broader scientific community and educate key stakeholders across healthcare systems.

Methods: A modified Delphi panel study was conducted to assess and fill gaps in key clinical topics in 1L DDLPS. We recruited a panel of sarcoma experts (N=12) with expertise in treating DDLPS and clinical trial design across Europe (France, Germany, Italy, Spain, UK, and Belgium) and the US. The study consisted of two rounds of anonymous surveys with pre-defined statements covering key questions. Surveys also included a request for feedback, which served to modify the statements on which consensus was not reached. Subsequently, revised statements were discussed in an unblinded consensus meeting to allow panel discussions, which resulted in a final list of agreed-upon statements.

Results: We tested 55 statements across different topics related to 1L DDLPS, including disease burden, treatment paradigm, unmet needs, PFS relevance as an endpoint, and cross-over trial design; consensus was reached on 43 statements. Experts agreed on 8 statements on disease burden, noting symptoms such as discomfort, abdominal distension, and fatigue among the most frequently reported. Experts reached consensus on 8 statements on treatment paradigm, agreeing that doxorubicin is the standard of care but acknowledging they are not fully satisfied with the treatment due to inadequate efficacy and frequent adverse events. Consensus was reached on 7 statements on unmet needs, highlighting diagnostic and referral challenges and the poor efficacy and safety of current treatments. Experts reached consensus on 15 statements on the relevance of PFS, agreeing that it is frequently used as a primary endpoint and that it is both clinically and patient relevant in 1L DDLPS. Lastly, experts agreed on 5 statements on the cross-over trial design, noting its ethical benefits and ability to adjust for cross-over effects in Overall Survival (OS) analyses. There were no statements where experts collectively disagreed.

Conclusion: This study shows that there is strong consensus around the high disease burden of DDLPS, which often leads to deterioration of patients’ quality of life. Experts agreed on the need for treatments with a better clinical profile, as they are not fully satisfied with the efficacy and safety of 1L treatments, including doxorubicin. Regarding the relevance of PFS, experts concluded that it is a direct measure of treatment effect and a good surrogate endpoint for survival benefit in 1L DDPLS, and therefore, that there is a clinically meaningful relationship between PFS and OS. On the cross-over clinical trial design, experts concluded it is well-accepted because it can encourage patient participation. Ultimately, there was alignment on key clinical endpoints and cross-over trial design being deemed appropriate and acceptable in 1L DDLPS. This study indicates that there is an alignment across geographies regarding the unmet need and treatment of DDLPS, and expectations for clinical trials. Raising awareness of DDLPS management and unmet needs, as well as the value of PFS and a cross-over clinical trial design, can contribute to improving patient outcomes and supporting the development of innovative treatments.