Yatagarasu: A single-arm, open-label, phase 2 study of apalutamide (APA) plus goserelin (GOS) for patients (pts) with far locally advanced or recurrent/metastatic (fLA/RM) and androgen receptor (AR)-expressing salivary gland carcinoma (SGC).

Abstract

6079 Background: Overexpression of AR is identified as a potential molecular target of SGC treatment. Combined androgen blockade (CAB) with bicalutamide has been evaluated previously, but the clinical usefulness of CAB with a next generation AR inhibitor has been unclear in SGC. We prospectively assessed the efficacy and safety of APA+GOS for pts with AR-expressing SGC. Methods: Eligible pts had fLA/RM SGC, and AR expression with at least 1% of cell nuclei immunohistochemistry staining positive. Pts were treated with APA 240 mg orally once daily and GOS 3.6 mg subcutaneously once 28 days. Primary endpoint was overall response rate (ORR) by central review according to RECIST v1.1, and a response (complete response [CR] or partial response [PR]) was confirmed by repeat assessments at least 4 weeks after the initial evaluation showing a response. Primary analysis was performed based on first 24 response evaluable (RE) pts who had been observed at least 24 weeks (Primary RE pts). The ORR was tested using exact test based on the binominal distribution, the null hypothesis for ORR of 14% was rejected when at least 8 of the 24 Primary RE pts were responders, and the efficacy was to be declared. Key secondary endpoints included clinical benefit rate (CBR), disease control rate (DCR), duration of response (DOR), and time to response (TTR) in the Primary RE pts, and overall survival (OS), progression free survival (PFS), and safety in the treated pts. Results: Twenty-six of the 31 pts treated with APA+GOS were regarded as RE by central review. For the 24 Primary RE pts, ORR was 25.0% (6/24), while 37.5% (9/24) including unconfirmed PR. Clinical benefit rate and DCR in the Primary RE pts were 50.0% and 70.8%, respectively. At the data cut-off (Apr 28, 2021), 5 of 6 pts with confirmed response were still on protocol treatment. Median PFS and OS in the treated pts were 7.43 months (mos) and not reached, respectively, with the median follow-up period of 8.57 mos. Grade 3 or higher treatment-related adverse events were reported in 4/31 (12.9%) pts, and the events were rash maculo-papular (n=2), anemia (n=1), and leukopenia (n=1). Conclusions: This is the first prospective trial evaluating CAB with APA for AR-expressing SGC. Although this study did not meet the predefined criteria of efficacy, clinically meaningful activity with well-tolerated safety profile of APA+GOS was shown. Clinical trial information: NCT04325828. [Table: see text]