Cediranib in Alveolar Soft-Part Sarcoma
In the phase II CASPS trial reported in The Lancet Oncology, Judson et al found evidence of activity of cediranib in alveolar soft-part sarcoma.
In the double-blind trial, 48 patients from 12 sites in the United Kingdom, Spain, and Australia were randomly assigned 2:1 between July 2011 and July 2016 to receive cediranib at 30 mg once daily (n = 32) or placebo (n = 16) for 24 weeks. Patients had to have metastatic alveolar soft-part sarcoma that had progressed in the previous 6 months, a life expectancy of more than 12 weeks, and could not have received anticancer treatment within 4 weeks prior to trial entry—with the exception of palliative radiotherapy.
Patients were unblinded to treatment at week 24 or sooner if progression occurred; those on placebo crossed over to cediranib, and all patients continued on open-label treatment until disease progression or death. Patients had a median age of 31 years, and 48% were female. The primary endpoint was percentage change in sum of target marker lesion diameters between baseline and week 24 or disease progression, if sooner, among evaluable patients.
Responses
A total of 44 patients were evaluable for the endpoint (28 in the cediranib group and 16 in the placebo group). Median follow-up was 34.3 months.
Median percentage change in sum of target marker lesion diameters among evaluable patients at 24 weeks was −8.3% in the cediranib group vs 13.4% in the placebo group (P = .0010). The best median percentage change in the sum of the diameters of target marker lesions by 24 weeks was –15.7% vs 1.2% (P < .0001). Among six patients with responses (all partial) to blinded cediranib treatment, the median duration of response was 16.0 months.
Adverse Events
The most common grade 3 adverse events with blinded cediranib treatment were hypertension (19%) and diarrhea (6%). A total of 15 serious adverse events were reported in 12 patients, with 12 of the events occurring during open-label treatment; the most common events were dehydration (n = 2), vomiting (n = 2), and proteinuria (n = 2). One death was considered probably related to treatment, due to intracranial hemorrhage at 41 days after an initial placebo patient started open-label cediranib.
The investigators concluded, “Given the high incidence of metastatic disease and poor long-term prognosis of alveolar soft-part sarcoma, together with the lack of efficacy of conventional chemotherapy, our finding of significant clinical activity with cediranib in this disease is an important step towards the goal of long-term disease control for these young patients. Future clinical trials in alveolar soft-part sarcoma are also likely to involve immune checkpoint inhibitors.”
Ian Judson, MD, of The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Cancer Research UK and AstraZeneca. For full disclosures of the study authors, visit thelancet.com.
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