In a phase II trial (Alliance A091404) reported in the Journal of Clinical Oncology, Ho et al found that enzalutamide showed some activity in advanced androgen receptor–positive salivary gland cancer but failed to meet the predefined criterion for a successful strategy.
Study Details
In the U.S. multicenter study, 46 patients with locally advanced/unresectable or metastatic disease enrolled between September 2016 and July 2018 received enzalutamide at 160 mg once daily in 28-day cycles. The primary endpoint was best overall response rate on Response Evaluation Criteria in Solid Tumors, version 1.1, within eight cycles, with best overall response consisting of complete responses and partial responses confirmed on imaging performed more than 4 weeks apart. The strategy was considered worthy of further investigation if confirmed responses were observed in at least 5 of 41 patients .
Responses
KEY POINTS
- Partial response was observed in 15% of patients but confirmed response in only 4%.
- Stable disease was observed in 52% of patients.
Objective responses (all partial) were observed in seven patients (15.2%), but only two (4.3%) met the criterion for confirmed response; thus, the study endpoint was not met. The durations of the two confirmed responses were 9.4 and 25.6 months. A total of 24 patients (52.2%) had stable disease. Partial response or stable disease ≥ 6 months was observed in 18 patients (39.1%). Tumor regression in target lesions was observed in 26 patients (56.5%).
Median progression-free survival was 5.6 months (95% confidence interval [CI] = 3.7–7.5 months) and median overall survival was 17.0 months (95% CI = 11.8–30.0 months). Median overall survival was 32.7 months (95% CI = 27.4 months to not estimable) among the 18 patients with progression-free survival ≥ 6 months vs 10.1 months (95% CI = 6.5–27.6 months) among the other 28 patients (P = .0004).
Adverse Events
The most common adverse events of any grade were fatigue (89%), hypertension (74%), hot flashes (48%), and weight loss (46%). The most common grade 3 or 4 adverse events were hypertension (20%), fatigue (9%), and hyponatremia (4%). Adverse events led to discontinuation of treatment in one patient. One patient died due to respiratory failure, considered unrelated to enzalutamide treatment. Total and free testosterone levels increased by a mean of 61.2% and 48.8%.
The investigators concluded: “Enzalutamide demonstrated limited activity in [androgen receptor–positive salivary gland cancer], 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.”
Alan Loh Ho, MD, PhD, Department of Medicine, Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The investigator-initiated study was supported by grants from the National Cancer Institute and by Astellas and Pfizer. For full disclosures of the study authors, visit ascopubs.org.
