Abiraterone Acetate in Patients With Castration-Resistant, Androgen Receptor-Expressing Salivary Gland Cancer: A Phase II Trial

Abstract

Purpose: The activity of androgen-deprivation therapy (ADT) in androgen receptor-positive (AR+) salivary gland carcinomas (SGCs) has been established in the past few years. Second-line treatment in castration-resistant patients is still unknown. We investigated the activity of abiraterone acetate as second-line treatment in ADT-resistant, AR+ patients with SGC.

Methods: This was a single-institution phase II trial. A two-stage Simon's design was applied. The primary end point was confirmed objective response rate. Secondary end points were disease control rate, safety, progression-free survival, and overall survival. Patients were eligible when the following criteria were met: histologic diagnosis of AR-overexpressing SGC, measurable disease according to RECIST 1.1, clinical and/or radiologic progression on ADT, suppressed serum testosterone, and no limits for the number of previous chemotherapy lines. All patients received abiraterone 1 g daily plus prednisone 10 mg and luteinizing hormone-releasing hormone agonist until progression or unacceptable toxicities.

Results: From 2015 to 2019, 24 AR+ patients with SGC (23 men; median age 65.8 years) were treated within the study. The overall response rate was 21% (5 partial responses), with a disease control rate of 62.5%. The median duration of response was 5.82 months. Median progression-free survival was 3.65 months (95% CI, 1.94 to 5.89), and median overall survival was 22.47 months (95% CI, 6.74 to not reached). Objective response to previous ADT did not correlate with the activity of abiraterone. Adverse events (AEs) were recorded in 22 cases (92%) with grade 3 AEs in six patients (25%): fatigue (two), flushing (one), supraventricular tachycardia (one), and two non-drug-related AEs. No drug-related grade 4 or 5 AEs were recorded.

Conclusion: Abiraterone plus luteinizing hormone-releasing hormone agonist is active and safe as a second-line option in AR-expressing, castration-resistant SGC.

Trial registration: ClinicalTrials.gov NCT02867852.

Conflict of interest statement

Laura D. LocatiHonoraria: McCann Health, BiogenConsulting or Advisory Role: Bristol Myers Squibb Foundation, Eisai, Lilly, Ipsen, MSD, Merck SeronoResearch Funding: EisaiTravel, Accommodations, Expenses: Eisai, BMS, Merck Serono, MSD Carlo ResteghiniHonoraria: Sun Pharma Paolo BossiHonoraria: Bristol Myers Squibb, Merck, Regeneron, GlaxoSmithKline, MSD OncologyConsulting or Advisory Role: Merck Serono, Bristol Myers Squibb, Sanofi/Regeneron, Angelini Pharma, MSD Oncology, Sun Pharma, GlaxoSmithKlineResearch Funding: Amgen, Merck Serono, Roche, MSD Oncology, GlaxoSmithKline, Regeneron Lisa LicitraConsulting or Advisory Role: Eisai, Boehringer Ingelheim, AstraZeneca, SOBI, Novartis, Bayer, MSD, Merck Serono, Roche, Bristol Myers Squibb, Incyte, Doxapharma, GlaxoSmithKline, Nanobiotix, Debiopharm Group, Amgen, Ipsen, RocheResearch Funding: AstraZeneca, Novartis, Roche, MSD, Eisai, Merck Serono, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Exelixis, IRX Therapeutics, Medpace, Pfizer, Debiopharm Group, RocheTravel, Accommodations, Expenses: Merck Serono, Bristol Myers Squibb, MSD, Eisai, AstraZenecaNo other potential conflicts of interest were reported.

Figures

FIG 1.

Swimmer plot showing the duration of treatment with abiraterone. PD, disease progression; PR, partial response.

FIG 2.

(A) PFS and (B) OS in the study population. OS, overall survival; PFS, progression-free survival.

FIG A1.

Case of a responding lung metastasis.

FIG A2.

Case of a responding liver metastasis.

FIG A3.

PFS and OS stratified according to histology (SDC v adenocarcinoma NOS): product-limit survival estimate of (A) PFS and (B) OS. NOS, not otherwise specified; OS, overall survival; PFS, progression-free survival; SDC, salivary duct carcinoma.