Background: Well-differentiated (WD) and dedifferentiated (DD) liposarcomas (LPS) are characterized by cyclindependent kinase (CDK)4 and mouse double minute 2 homolog (MDM2) amplification.Palbociclib, a selective CDK4/6 inhibitor, demonstrated promising activity in prior phase II trials and is included in the National Comprehensive Cancer Network Compendium for LPS.However, long-term overall survival (OS) data remain limited.Patients and methods: Patients with advanced WD/DD LPS were enrolled in two non-randomized phase II trials.Cohort A received palbociclib 200 mg (14 days on, 21-day cycle); cohort B received 125 mg (21 days on, 28-day cycle).Kaplan-Meier methods were used to estimate progression-free survival (PFS) and OS.Baseline factors and subsequent anticancer therapies were evaluated for association with outcomes.Results: Among 90 patients, 88 were assessable for PFS.Median follow-up was 3.12 years (cohort A) and 2.59 years (cohort B).Median PFS was 4.2 and 4.1 months, and median OS was 26.0 and 24.2 months in cohorts A and B, respectively.One-and two-year OS rates exceeded 70% and 50%, respectively, across cohorts.Patients with pure WD histology (n = 15) had longer PFS (hazard ratio 0.53, P = 0.037) but no OS difference.Cadherin 18 (CDH18) expression on baseline tumor tissue was associated with improved PFS (P = 0.007) and OS (P = 0.003).After treatment, 39% underwent surgery and 46% received additional systemic therapy.Conclusions: This study provides the longest prospective OS data for palbociclib in WD/DD LPS.CDK4/6 inhibition remains a relevant treatment option, especially for patients unsuitable for cytotoxic therapy.CDH18 expression was associated with clinical outcomes and represents an exploratory biomarker signal that warrants independent validation in future prospective, biomarker-focused studies.
Babatunde et al. (Fri,) studied this question.