LH–RH agonist monotherapy for androgen receptor-positive recurrent and/or metastatic salivary gland cancer: a retrospective study

Background: Although combination therapy consisting of a luteinizing hormone–releasing hormone (LH–RH) agonist and an Androgen receptor (AR) inhibitor has demonstrated promising clinical activity for recurrent and/or metastatic SGC (R/M SGC), few studies on LH–RH agonist monotherapy have been reported. Methods: We conducted a retrospective analysis of patients with AR-positive, R/M SGC treated by monotherapy with LH–RH agonists in our institution from November 2004 to July 2023. Results: Nineteen patients were identified; the median age was 64 years (range 42–82), 10 had salivary duct carcinoma (52.6%), and 3 had adenocarcinoma, not otherwise specified (15.8%). LH–RH agonist monotherapy was delivered as first-line systemic therapy for R/M disease in 16 patients (84.2%). Nine patients (47.4%) achieved tumor size reduction in target lesions with a median tumor shrinkage of 11% (range 1–100%), resulting in an overall response rate and clinical benefit rate (rate of patients achieving a complete response, partial response, or stable disease lasting for at least 24 weeks) of 15.8% and 36.8%, respectively. The median duration of treatment with LH–RH agonist monotherapy was 5.1 months (range 0.3–63.4), accounting for 35.2% of the entire treatment period. Median progression-free survival and overall survival was 3.2 months (95% confidence interval (95% CI), 1.6–6.0) and 21.6 months (95% CI 9.9–34.4), respectively. No severe adverse events leading to treatment interruption or discontinuation were seen. Conclusion: LH–RH agonist monotherapy demonstrated a well-balanced profile between efficacy and safety and could be an alternative therapeutic option, especially for subjects not tolerable to combination therapy. (242 words).