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

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.

Figure 1.

CONSORT diagram of the two-arm randomized trial. Patients were randomly assigned to either the cediranib arm or the sunitinib arm. Crossover was allowed at disease progression.

Figure 2.

Number of cycles of therapy for each of the evaluable 29 patients on the study based on their initial therapy: cediranib (A) or sunitinib (B). Prior therapy is indicated next to patient ID: s, surgery; c, chemotherapy; r, radiation. Two patients achieved a PR in at least one arm of the study, before/and after crossover. C, Median PFS for all 34 patients based on initial therapy arm assignment.

Figure 3.

Percentage change from baseline in tumor size over time for patients with ASPS receiving cediranib as initial therapy (A), cediranib as second therapy (B), sunitinib as initial therapy (C), and sunitinib as second therapy (D). PR, partial response. Dotted lines represent the thresholds for PR and progressive disease according to RECIST 1 guidelines.