The androgen biosynthesis inhibitor, abiraterone acetate, in combination with luteinizing hormone-releasing hormone (LHRH) agonist was found to be safe and active as a second-line option in castration-resistant, androgen receptor (AR)-positive patients with salivary gland carcinoma (SGC), according to results of a phase 2 trial published in the Journal of Clinical Oncology.
SGCs are rare head and neck malignancies for which there are no standard drug therapies. More than 90% of patients with SGC are androgen receptor (AR)-positive, allowing for new treatment options for these rare tumors.
Abiraterone is approved for the treatment of metastatic castration-resistant prostate cancer in patients who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy (ADT).
ADT has been shown to benefit patients with AR-positive SGC. However, there are no other therapeutic options other than palliative chemotherapy for progression after ADT, highlighting the unmet need for alternative therapeutic approaches.
In a single-institution, phase 2, European trial (ClinicalTrials.gov Identifier: NCT02867852), researchers evaluated the efficacy of abiraterone acetate as second-line treatment in ADT-resistant, AR-positive patients with SGC.
The primary endpoint was confirmed overall response rate (ORR). Secondary endpoints included disease control rate, progression-free survival (PFS), overall survival (OS), and safety.
Between 2015 and 2019, the study enrolled 24 patients with AR-positive SGC, of whom 23 were men. The median age of the patients was 65.8 years (range, 44-77 years), and the median follow-up was 9.47 months.
Patients were treated with 1 g abiraterone acetate, which was given as four 250 mg tablets daily, along with 5 mg of oral prednisone twice a day. During treatment with abiraterone, patients received LHRH analogs to suppress testosterone levels to 50 ng/dL.
The ORR was 21%, which included 5 partial responses. The disease control rate was 62.5%. The median duration of response was 5.82 months.
The median PFS was 3.65 months (95% CI, 1.94-5.89), and the median OS was 22.47 months (95% CI, 6.74-not reached). The objective response to previous ADT did not correlate with the activity of abiraterone.
The 1-year OS rate was 66.59% (74.48% in 19 patients with SDC and 50% in 5 patients with adenocarcinoma not otherwise specified, P =.334). The median OS from diagnosis of primary SGC was 94.31 months (95% CI, 46.61-not reached).
At least 1 adverse event (AE) was reported in 22 cases (92%). Grade 3 AEs occurred in 6 cases (25%), 4 of which were drug-related (2 fatigue, 1 flushing, and 1 supraventricular tachycardia) and 2 of which were not drug-related (1 cancer-related pain and 1 xerostomia).
There were no grade 4 or 5 drug-related AEs. None of the patients required dose reductions or discontinued the trial because of toxicity.
“Abiraterone acetate plus prednisone and luteinizing hormone-releasing hormone analog can be considered as a valid and safe therapeutic option for androgen receptor-positive patients with SGC in second line after failure of ADT,” the researchers wrote. “The assessment of the molecular phenotype in these patients could provide further biologic details on mechanisms of response and ADT resistance.”
Disclosure: This research was supported by Janssen Pharmaceuticals, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Locati LD, Cavalieri S, Bergamini C, et al. Abiraterone acetate in patients with castration-resistant, androgen receptor-expressing salivary gland cancer: A phase II trial. J Clin Oncol. Published online October 1, 2021. doi:10.1200/JCO.21.00468