Combined androgen blockade in patients with advanced androgen receptor-positive salivary gland carcinoma: Exploratory biomarker analyses

Abstract

Background: A phase II trial of combined androgen blockade (CAB) in patients with advanced androgen receptor (AR)–positive salivary gland carcinoma (SGC) showed 40% of the overall response rate. However, biomarkers which predict survival in this population remain unknown. Methods: A total of 99 patients with AR–positive SGC treated with leuprorelin acetate plus bicalutamide were included. Age, sex, ECOG performance status (PS), previous treatment with trastuzumab plus docetaxel, modified Glasgow Prognosis Score (mGPS), neutrocyte-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), serum C-reactive protein (CRP) and testosterone level, HER2 status (according to ASCO/CAP Guidelines), mutational status of BRAF, PIK3CA, HRAS, AKT1 and TP53, immunohistochemistry (IHC) score of AR, Ki-67, CK5/6, p53, HER3, Akt, PI3K, FOXA1, adipophilin, mTOR and PTEN were assessed and correlated with progression-free survival (PFS) and overall survival (OS). Results: Female sex, mGPS (1 or 2 vs. 0), NLR (≥4.48), PLR (≥234.27), and Ki-67 labeling index (≥ 40%) were significantly associated with shorter PFS (hazard ratio [HR], 3.57, 2.01, 1.76, 1.62, and 2.16, respectively) and OS (HR, 4.91, 4.98, 3.10, 2.95, and 1.78, respectively). IHC scores of PTEN (3+) and adipophilin (≥5%) were related with favorable PFS (HR, 0.57 and 0.49, respectively) and OS (HR, 0.48 and 0.42, respectively). Age, ECOG PS, CRP, testosterone, AR positive ratio (≥70% or < 70%), HER2 status, previous treatment with trastuzumab plus docetaxel, FOXA1 immunopositivity, and mutational status of BRAF, PIK3CA, HRAS, and TP53 did not have significant association with survival. Conclusions: Rather than age and PS, sex and higher inflammation-based prognostic scores can serve as predictive biomarkers in patients with advanced SGC treated with CAB. IHC assessment of Ki-67, PTEN, and adipophilin may predict survival of this population. Biological validation of such markers is warranted. Clinical trial identification: UMIN000009437, Released on 03/12/2012. Legal entity responsible for the study: The authors. Funding: MEXT/JSPS. Disclosure: All authors have declared no conflicts of interest.