Overall survival from the open label phase 2 trial of palbociclib in patients with advanced well differentiated/dedifferentiated liposarcoma.

Abstract

11552 Background: Liposarcomas (LPS) are among the most common soft tissue sarcoma subtypes. Well-differentiated (WD) and dedifferentiated (DD) LPS are characterized by CDK4 and MDM2 amplification. Both subtypes have variable sensitivity to chemotherapy. However, effective systemic treatment options remain limited for unresectable or metastatic disease. Our group previously reported two phase 2 trials of the CDK4/6 inhibitor (CDK4/6i) palbociclib (PD0332991) in advanced WD/DD LPS, which established proof-of-concept for targeting CDK4 in this disease. Palbociclib demonstrated prolonged progression-free survival (PFS) and was included in the NCCN Compendium for LPS. However, prospective data on overall survival (OS) in this population remain limited. We now report OS analysis approximately 8.5 years after the last patient was enrolled. Methods: Patients with advanced WD/DD LPS were enrolled in two non-randomized phase 2 trials of palbociclib: cohort A received 200 mg daily for 14 days on a 21-day cycle, while cohort B received 125 mg daily for 21 days on a 28-day cycle. Survival outcomes were analyzed using Kaplan-Meier methods, and baseline factors were evaluated for association with PFS and OS. Subsequent anti-cancer therapies, including surgery and systemic treatments, were recorded and analyzed. Results: Among 90 enrolled patients, 88 were evaluable for PFS. Median follow-up was 17 months for cohort A and 21 months for cohort B. Updated median PFS was 18.2 weeks (95% CI: 17.7–36.4 weeks) in cohort A and 18.8 weeks (95% CI: 12–23.4 weeks) in cohort B. Median OS was 25.6 months (95% CI: 17.2–40.0 months) in cohort A and 24.1 months (95% CI: 17.5–38.4 months) in cohort B. Across both cohort, patients with pure WD histology were underrepresented, comprising 15 of the 90 patients. Patients with pure WD histology demonstrated longer PFS compared to patients with DD or WD/DD histology (HR: 0.55; 95% CI: 0.30–0.99). However, no significant difference in OS was observed between histologic groups (HR: 0.64; 95% CI: 0.35–1.16). Surgery was performed on 35 patients (39%) post-palbociclib, of which 5 patients had pure WD histology. Analyses on subsequent therapies, including surgery and systemic treatments, will be presented at the meeting. Conclusions: This study provides updated long-term outcomes for palbociclib in advanced WD/DD LPS. Palbociclib demonstrated consistent PFS and OS across dosing regimens, offering a tolerable alternative to chemotherapy for patients who may not be candidates for cytotoxic agents. While PFS and OS outcomes remain modest, these data reaffirm the role of CDK4/6i in the management of this disease and underscore the need for novel therapeutic strategies. Future efforts should focus on biomarker-driven approaches and combination therapies to optimize outcomes in this challenging disease. Clinical trial information: NCT01209598 .