A prospective phase II study of combined androgen blockade in patients with androgen receptor-positive metastatic or locally advanced unresectable salivary gland carcinoma

Abstract

BackgroundThere is no standard first-line chemotherapy for recurrent/metastatic (RM) or unresectable locally advanced (LA) salivary gland carcinoma (SGC). Patients and methodsWe conducted a single institution, open-label, single arm, phase II trial of combined androgen blockade (CAB) for androgen receptor (AR)-positive SGC. Leuprorelin acetate was administered subcutaneously at a dose of 3.75mg every 4weeks. Bicalutamide was administered orally at a daily dose of 80mg. Patients were treated until progressive disease or unacceptable toxicities. ResultsThirty-six eligible patients were enrolled. Thirty-three patients had RM disease and three patients had LA disease. The pathological diagnoses were salivary duct carcinoma (34 patients, 94%) and adenocarcinoma, NOS (two patients, 6%). The best overall response rate was 41.7% [n=15, 95% confidence interval (CI), 25.5%–59.2%], the clinical benefit rate was 75.0% (n=27, 95% CI, 57.8%–87.9%). The median progression-free survival was 8.8months (95% CI, 6.3–12.3months) and the median overall survival was 30.5months (95% CI, 16.8months to not reached). Additional analyses between treatment outcomes and clinicopathological factors or biomarkers including AR positivity, human epidermal growth factor receptor 2 status, and its complex downstream signaling pathway gene mutations showed no statistically significant differences. Elevated grade 3 liver transaminases and increased serum creatinine were reported in two patients, respectively. Discontinuation of leuprorelin acetate or bicalutamide due to adverse event occurred in one patient. ConclusionThis study suggests that CAB has equivalent efficacy and less toxicity for patients with AR-positive RM or unresectable LA SGC compared with conventional chemotherapy, which warrants further study. Clinical Trial RegistrationUMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703