Randomized Phase II Trial of Sunitinib or Cediranib in Alveolar Soft Part Sarcoma

Clin Cancer Res. 2023 Apr 3;29(7):1200-1208. doi: 10.1158/1078-0432.CCR-22-2145.

Abstract

Purpose: Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor with few treatment options. We designed a phase II randomized trial to determine the activity and tolerability of single-agent cediranib or sunitinib in patients with advanced metastatic ASPS.

Patients and methods: Patients 16 years of age and older were randomized to receive cediranib (30 mg) or sunitinib (37.5 mg) in 28-day cycles. Patients could cross over to the other treatment arm at disease progression. The primary endpoint was to measure the objective response rate (ORR) for each agent. Median progression-free survival (mPFS) for the two arms was also determined.

Results: Twenty-nine of 34 enrolled patients were evaluable for response. One patient on each of the initial two treatment arms had a partial response (ORR: 6.7% and 7.1% for cediranib and sunitinib, respectively). Twenty-four patients had a best response of stable disease (86.7% and 78.6% for cediranib and sunitinib, respectively). There were no significant differences in mPFS for the two treatment arms. Clinical benefit (i.e., objective response or stable disease for a minimum of four or six cycles of therapy) on the first-line tyrosine kinase inhibitor (TKI) therapy did not predict benefit on the second-line TKI. Both drugs were well tolerated. As of August 2021, 1 patient (unevaluable for ORR) remains on study.

Conclusions: The study did not meet its endpoints for ORR. Although both TKIs provided clinical benefit, the outcomes may have been attenuated in patients who had progressed ≤6 months before enrollment, potentially accounting for the low response rates. See related commentary by Wilky and Maleddu, p. 1163.

Publication types

  • Editorial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Comment

MeSH terms

  • Humans
  • Indoles / adverse effects
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Quinazolines / therapeutic use
  • Sarcoma, Alveolar Soft Part* / drug therapy
  • Sarcoma, Alveolar Soft Part* / pathology
  • Sunitinib / adverse effects

Substances

  • Sunitinib
  • cediranib
  • Indoles
  • Quinazolines
  • Protein Kinase Inhibitors