Phase II study of enzalutamide for patients with androgen receptor-positive salivary gland cancers (Alliance A091404) Journal Article
| Authors: | Ho, A. L.; Foster, N. R.; Zoroufy, A. J.; Campbell, J. D.; Worden, F.; Price, K.; Adkins, D.; Bowles, D. W.; Kang, H. Y. S.; Burtness, B.; Sherman, E.; Morton, R.; Morris, L. G. T.; Nadeem, Z.; Katabi, N.; Munster, P.; Schwartz, G. K. |
| Article Title: | Phase II study of enzalutamide for patients with androgen receptor-positive salivary gland cancers (Alliance A091404) |
| Abstract: | PURPOSEThe androgen receptor (AR) is expressed (+) in a subset of salivary gland cancers (SGCs). This phase II trial evaluated the efficacy of the antiandrogen enzalutamide in AR+ SGC.METHODSPatients with locally advanced/unresectable or metastatic AR+ SGCs were enrolled. Enzalutamide (160 mg) was given orally once daily. The primary end point was the best overall response rate per RECIST v1.1 within eight cycles. Confirmed responses in >= 5 of 41 patients would be considered promising. Secondary end points were progression-free survival, overall survival, and safety.RESULTSForty-six patients were enrolled; 30 (65.2%) received prior systemic therapy, including 13 (28.3%) with AR-targeted drugs. Of seven (15.2%) partial responses (PRs), only two (4.3%) were confirmed per protocol and counted toward the primary end point. Twenty-four patients (52.2%) had stable disease; 15 (32.6%) had progression of disease as best response. Twenty-six patients (56.5%) experienced tumor regression in target lesions; 18 (39.1%) had partial response/stable disease >= 6 months. Tumor regressions were observed in female patients (5 of 6 [83.3%]) and those who received prior AR- (6 of 13 [46.2%]) or human epidermal growth factor receptor 2-targeted therapies (5 of 8 [62.5%]). Three patients remained on treatment at data cutoff (duration, 32.2-49.8 months). The median progression-free survival was 5.6 months (95% CI, 3.7 to 7.5); the median overall survival was 17.0 months (95% CI, 11.8 to 30.0). The most common adverse events were fatigue, hypertension, hot flashes, and weight loss. Total and free testosterone levels increased by a mean of 61.2% and 48.8%, respectively, after enzalutamide.CONCLUSIONEnzalutamide demonstrated limited activity in AR+ SGC, failing to meet protocol-defined success in part because of a lack of response durability. Strategies to enhance the efficacy of antiandrogen therapy are needed. |
| Keywords: | monotherapy; castration; molecular characterization; expression; efficacy; activation; inhibition; duct carcinoma; open-label; metastatic prostate-cancer |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 40 |
| Issue: | 36 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2022-12-20 |
| Start Page: | 4240 |
| End Page: | 4249 |
| Language: | English |
| ACCESSION: | WOS:000940363000010 |
| DOI: | 10.1200/jco.22.00229 |
| PROVIDER: | wos |
| PMCID: | PMC9916043 |
| PUBMED: | 35867947 |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding author is MSK author Alan Loh Ho -- Source: Wos |
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