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Palbociclib in Patients With Soft Tissue Sarcoma With CDK4 Amplifications: Results From the Targeted Agent and

Scott Schuetze1, Michael Rothe2, Pam K Mangat2

  • 1Department of Internal Medicine, University of Michigan, Ann Arbor, MI.

JCO Precision Oncology
|July 16, 2024
PubMed
Abstract

Insights

Palbociclib showed antitumor activity in soft tissue sarcoma patients with CDK4 amplification. The drug demonstrated a 46% disease control rate, meeting trial criteria for efficacy in this targeted therapy trial.

Area of Science:

  • Oncology
  • Genomics
  • Pharmacology

Background:

  • The Targeted Agent and Profiling Utilization Registry (TAPUR) trial investigates targeted therapies in advanced cancers with specific genomic alterations.
  • Soft tissue sarcoma (STS) is a heterogeneous group of cancers, and identifying actionable genomic alterations is crucial for treatment selection.

Purpose of the Study:

  • To evaluate the antitumor activity of palbociclib, a targeted agent, in patients with advanced soft tissue sarcoma harboring cyclin-dependent kinase 4 (CDK4) amplification.
  • To assess disease control, response rates, survival outcomes, and safety of palbociclib in this specific patient cohort.

Main Methods:

  • A phase II basket trial design was employed, enrolling patients with measurable disease and adequate performance status.
  • The primary endpoint was disease control (DC), defined as objective response (OR) or stable disease (SD) for at least 16 weeks (SD16+), assessed by RECIST v1.1.
  • Secondary endpoints included OR, progression-free survival (PFS), overall survival (OS), and safety assessments.

Main Results:

  • Forty-two patients with CDK4-amplified STS were enrolled; one was not evaluable for efficacy.
  • The disease control rate was 46% (90% CI, 36-100), with one partial response and 18 patients achieving SD16+.
  • Median PFS was 16 weeks (95% CI, 9-28) and median OS was 69 weeks (95% CI, 31-111). Grade 3-4 adverse events possibly related to palbociclib occurred in 20 patients, with no serious events reported.

Conclusions:

  • Palbociclib demonstrated a signal of antitumor activity in patients with soft tissue sarcoma and CDK4 amplification.
  • The drug met the prespecified criteria for efficacy within the TAPUR trial for this specific molecularly defined subgroup.

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