Cediranib Reduces Tumor Burden in Sarcoma

Ian Judson, MD

Cediranib was associated with significantly reduced tumor burden and superior progression-free survival compared with placebo in patients with alveolar soft part sarcoma (ASPS).

In phase II results from the international, double-blind, randomized CASPS trial presented at the 2017 ASCO Annual Meeting, cediranib, an oral antiangiogenic inhibitor of VEGFR 1-3, reduced target marker lesions by 8.3% (IQR, 26.5-5.9) from baseline at 24 weeks. In contrast, placebo was associated with a 13.4% increase (IQR, 0.6-23.1; P = .001).

Median progression-free survival (PFS) was 10.8 months versus 3.7 months in favor of cediranib, but that outcome fell slightly short of significance (HR, 0.58; 90% CI, 0.33-1.03; P = .059). At 12 months, PFS in the experimental group was double that of placebo, 47.7% versus 22.5%.

“I’m delighted to be able to present these data. When we set out to do a study in such a rare disease with a clinical trial design, we questioned our sanity,” said Ian Judson, MD, consultant medical oncologist, the Royal Marsden NHS Foundation Trust. Judson presented an analysis based on a data snapshot taken May 25.

He went on to say, “CASPS confirms the significant activity of cediranib against ASPS, which has previously been demonstrated in single-arm phase II trials.”

ASPS is an extremely rare disease, with 12 to 14 diagnoses per year in the United Kingdom. It appears most often in adolescents and children, and is characterized by a high rate of metastases, long latency, slow progression, and spontaneous stabilization or regression.

Investigators recruited 48 patients with progressive, metastatic disease at 12 sites in Australia, Spain, and the United Kingdom from July 2011 to July 2016. Median age was 31 and 52% of patients were women. All patients were ECOG status 0 or 1.

Sixteen patients were assigned to placebo and 32 were assigned to 30 mg of cediranib daily. The study was unblinded at 24 weeks or progression, whichever came first, and patients who progressed were assigned to cediranib. Patients in the placebo group who had not progressed by 24 weeks were then allowed to cross over and continue treatment until progression or death.

A total of 28 patients assigned to cediranib and all 16 patients in the placebo group were eligible for evaluation. One patient in each group had undergone prior cediranib therapy.

Among patients who were cediranib-naïve, the drug reduced target marker lesions by 4.4% (IQR, 26.3-6.0) from baseline at 24 weeks. Placebo was associated with a 14.4% increase (IQR, 2.3-23.5; P = .0019).

At 24 weeks, the best response in the cediranib group was partial response (n = 3; P = .29), with 14 patients with stable disease and 11 patients who progressed. There were 7 patients with stable disease in the placebo group and 9 patients who progressed.

“If we look at response duration, 3 patients who had a partial remission still have not progressed,” Judson said. “The median duration of response is in excess of 26 months for the responding patients.

Twelve patients assigned to cediranib had received prior TKI therapy. Judson said prior therapy did not appear to affect PFS, except for patients previously treated with crizotinib (Xalkori; n = 5), who seemed to have slightly poorer outcomes.

Median overall survival (OS) had not been reached, but OS at 12 months favored the cediranib arm (94.0% vs 66.0%; HR, 0.66; 95% CI, 0.25-1.75; P = .41). There were 10 (31.3%) OS events in the experimental arm compared with 7(43.8%) in the placebo arm.

Patients assigned to cediranib experienced significantly more adverse events (AEs). The most common grade ≥3 AE in the cediranib group was hypertension (19.4%) followed by increased GGT (6.5%) and diarrhea (6.5%). There were 3 cases of grade ≥3 AEs in the placebo group—1 incident of increased GGT (6.3%) and 2 incidents of dyspnea (12.5%).

William L. Read, MD, associate professor, Department of Hematology and Medical Oncology, Emory University School of Medicine—Winship Cancer Institute, reviewed the data for OncLive. He is participating in a phase II study currently in recruitment that will evaluate the safety and efficacy of the anti—PD-L1 antibody atezolizumab (Tecentriq) and said he is more excited about the possibilities of immunotherapy for patients with ASPS.

“It’s no surprise that cediranib showed efficacy against ASPS, given that sunitinib (Sutent), pazopanib (Votrient), and bevacizumab (Avastin) all work in this space—sometimes,” he said. “The question is whether cediranib is better, or safer, or cheaper? Does it work longer or does it work when something else, such as sunitinib, has failed? Hopefully one or more of those questions will be addressed in the full publication.”

Judson IR, Morden JP, Leahy MG, et al. Activity of cediranib in alveolar soft part sarcoma (ASPS) confirmed by CASPS (cediranib in ASPS), an international, randomised phase II trial (C2130/A12118). J Clin Oncol. 35, 2017 (suppl; abstr 11004).