trelstar and Salivary-Gland-Neoplasms

Androgen deprivation therapy has some clinical activity in selected salivary gland cancer histotypes, with androgen receptor expression.. We retrospectively analyzed patients with androgen receptor-expressing recurrent/metastatic salivary gland cancer, treated with androgen deprivation therapy. Protein expression of androgen receptor and ErbB family members was investigated. Progression-free survival (PFS) and overall survival (OS) were the main endpoints.. Seventeen patients were identified. No significant toxicities were reported. Overall response rate was 64.7%; 3-year PFS and 5-year OS were 11.8% and 19.3%, respectively. Androgen receptor overexpression may be sustained by gain of chromosome X (58%) and TP53 mutation (44%). No association between response to androgen deprivation therapy and epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)2, HER3 expression, PIK3CA mutations, or phosphatase and tensin homolog (PTEN) deletion was identified.. We confirm the activity of androgen deprivation therapy in androgen receptor-expressing recurrent/metastatic salivary gland cancers. The hypothesis that an androgen receptor increased gene copy number may represent a possible mechanism of primary resistance should be further investigated.

Topics: Adult; Aged; Androgen Antagonists; Anilides; Biomarkers; DNA Mutational Analysis; ErbB Receptors; Female; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Male; Middle Aged; Neoplasm Recurrence, Local; Nitriles; Receptors, Androgen; Retrospective Studies; Salivary Gland Neoplasms; Survival Analysis; Tosyl Compounds; Treatment Outcome; Triptorelin Pamoate

Androgen-deprivation therapy (ADT) has been reported to be active in androgen receptor (AR)-expressing, relapsed/metastatic (RM), salivary gland cancers (SGCs). Abiraterone, an inhibitor of androgen synthesis, has recently been approved as a second-line treatment in hormone-resistant (HR) prostate cancer (PCa) patients. Two patients with AR-positive HR-RM adenocarcinoma, NOS of the salivary glands have been treated with abiraterone. This is the first time that this agent has been reported to be active in tumors other than HRPCa. Immunohistochemical analysis showed overexpression of EGFR, HER2, and HER3 in both untreated primary tumors. Sequencing analysis revealed a TP53 non-functional mutation in one case and a PIK3CA-activating mutation in the other. In conclusion, second line activity of ADT in AR-expressing, adenocarcinoma, NOS of salivary glands further strengthens the pathogenic and therapeutic role of AR signaling in AR-positive SGCs.

Topics: Adenocarcinoma; Adult; Androgen Antagonists; Androstenes; Androstenols; Anilides; Antineoplastic Agents, Hormonal; Drug Resistance, Neoplasm; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms, Hormone-Dependent; Nitriles; Receptors, Androgen; Salivary Gland Neoplasms; Tosyl Compounds; Treatment Outcome; Triptorelin Pamoate