Androgen Receptor‐Targeted Therapy for Salivary Gland Carcinoma: Systematic Review and Meta‐Analysis
J. Walker Rosenthal, David Z. Allen, Jordan Sternthal, Isabella Romeo, Gurel Ari, Brianna Brammer, Erin E. Reardon, Jose A. Monteiro de Oliveira Novaes, Nabil F. Saba, Jennifer Gross, Nicole C. SchmittABSTRACT
Objective
Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with limited effective treatment options in the recurrent/metastatic setting. Biologically, SDC has high rates of androgen receptor (AR) expression, providing a strong rationale for AR‐targeted therapy.
Data Sources
Ovid MEDLINE,
Review Methods
We conducted a systematic review and meta‐analysis of AR‐targeted therapy in patients with AR‐positive recurrent/metastatic SDC and SDC‐enriched salivary gland carcinoma cohorts. The primary outcome was overall response rate (ORR). Secondary outcomes included clinical benefit rate (CBR), progression‐free survival (PFS), and overall survival (OS). Pooled proportions were calculated using a random‐effects model. Combined androgen blockade was compared to AR‐targeted monotherapy.
Results
Twelve studies were included in the systematic review accounting for 587 eligible patients. The primary meta‐analysis has 10 eligible studies (417 patients). The pooled ORR was 26.6% (95% CI, 15.4%–42.1%). Five studies reported CBR, and the pooled CBR was 45.0% (95% CI, 38.1%–52.1%). The sample‐size‐weighted mean of reported median PFS was 6.3 months, and the weighted mean of reported median OS was 26.9 months among the seven studies reporting OS. ORR was higher with combined androgen blockade than with AR‐targeted monotherapy (36.3% vs. 8.9%; meta‐regression p = 0.023).
Conclusion
AR‐targeted therapy shows clinically meaningful activity in AR‐positive disease, particularly with combined androgen blockade. The evidence remains heterogeneous and largely nonrandomized, so treatment decisions should account for HER2 status, AR expression level, treatment line, and patient tolerance.