Enzalutamide is a common first-line choice for patients with metastatic castration-resistant prostate cancer, but response in some patients eventually wanes and then patients are switched to a different treatment. According to the phase IIIb PRESIDE trial, reported at the 2022 ASCO Genitourinary Cancers Symposium, continuing enzalutamide in patients who experienced disease progression with enzalutamide and were given docetaxel and prednisone showed a statistically significant 1.25-month improvement in progression-free survival vs docetaxel and prednisone alone.1 These findings may offer a treatment option for some patients who have disease progression on enzalutamide.
Median progression-free survival was 9.5 months with continued enzalutamide vs 8.3 months with placebo (P = .027). Enzalutamide delayed the time to prostate-specific antigen (PSA) progression: 8.4 months vs 6.2 months in the placebo arm (P = .002).
“These data suggest that continued treatment with enzalutamide plus docetaxel offers a clinical benefit and could be a future treatment option for some patients who experience disease progression on enzalutamide alone,” said presenting author Axel S. Merseburger, MD, Chairman of the Clinic of Urology at University Hospital Schleswig-Holstein, Lübeck, Germany. “Continuous enzalutamide could be a treatment option to offer to the right patient,” he emphasized.
Commenting on these results from the PRESIDE trial, Oliver Sartor, MD, said: “The differences in progression-free survival are modest. This study is not a game-changer. Upon review of the data, it is evident that continuous enzalutamide does not substantially alter disease progression in men with metastatic castration-resistant prostate cancer who experience disease progression on enzalutamide.” Dr. Sartor is Assistant Dean for Oncology and Professor at Tulane School of Medicine, New Orleans.
The PRESIDE investigators hypothesized that continued targeting of the androgen receptor with enzalutamide could be of benefit beyond disease progression by controlling the tumor environment and allowing docetaxel to exert its effect on tumor growth.
The double-blind, open-label, randomized PRESIDE trial enrolled 687 patients in period 1, when open-label enzalutamide was given. Patients who had no PSA response or who were primary resistant were not eligible for period 2, during which remaining patients were randomly assigned in a 1:1 ratio to receive enzalutamide (n = 134) or placebo (n = 135). All patients received docetaxel and prednisone. Enzalutamide was given at 160 mg daily; docetaxel, at 75 mg/m2 every 3 weeks; and prednisone, at 10 mg every day. Treatment was continued until disease progression.
“Baseline characteristics of both treatment arms were largely similar for period 2,” Dr. Merseburger noted.
The median age was about 70 years. The median baseline PSA levels were 36.9 ng/mL for the enzalutamide group vs 28.1 ng/mL for the placebo group. More than 97% of patients were White. The Gleason score was 8 in about 56%. The sites of metastasis were similar between the groups, with 41.9% in the enzalutamide group and 34.8% in the placebo group having bone lesions and 21.3% and 17.8%, respectively, visceral metastases. Both bone and visceral metastases were present in 36.8% and 47.4%, respectively.
Key Results and Toxicity
The study met its primary endpoint for time to disease progression: 9.5 months for enzalutamide vs 8.3 months for placebo. Subgroup analysis showed consistent results with those in the overall study population. Progression-free survival was not significantly different between treatment arms for patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 or by sites of metastatic disease (ie, bone alone, viscera alone, or both sites).
PSA levels decreased from baseline to week 13 by 37.1% in the enzalutamide group compared with 9.1% in the placebo group.
The objective response rate was 31.6% in the enzalutamide group and 25.9% in the placebo group. Complete responses were observed in 26 patients in the enzalutamide group vs 17 in the placebo group. Partial responses were also observed in 17 and 18 patients, respectively.
The safety profile of enzalutamide was consistent with that of previous reports. Serious treatment-emergent adverse effects occurred in 49.3% of patients given enzalutamide and 38.5% given placebo. Adverse events leading to treatment discontinuation occurred in 8.8% and 6.7%, respectively. Deaths due to any cause occurred in 9.6% and 5.2%, respectively.
The most common treatment-emergent adverse events with enzalutamide vs placebo were asthenia (34.6% vs 25.9%), neutropenia (33.8% vs 33.3%), and alopecia (32.4% vs 27.4%). Median exposure to enzalutamide was 36.1 weeks vs 30.1 weeks with placebo.
Elisabeth Heath, MD, FACP, was the formal discussant of the PRESIDE trial. She is a member of the Genitourinary Oncology Multidisciplinary Team at Karmanos Cancer Institute and Professor at Wayne State University School of Medicine, Detroit. Dr. Heath stated: “Continuous enzalutamide is a treatment option, but it is not a standard of care. Would I be comfortable if a patient had responded to enzalutamide continuing enzalutamide and adding docetaxel? Yes, it is an option for the right patient.”
DISCLOSURE: Dr. Merseburger has received honoraria from Astellas Pharma, Bristol Myers Squibb, Eisai, Ipsen, Janssen-Cilag, Novartis, Pfizer, Roche, and Takeda; has served as a consultant or advisor to Astellas Pharma, Bristol Myers Squibb, Clovis Oncology, Ipsen, Janssen-Cilag, MSD Oncology, and Takeda; has served on the speakers bureau for Ipsen; has received institutional research funding from AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Janssen-Cilag, and Novartis; and has received reimbursement for travel, accommodations, and expenses from Astellas Pharma, Ipsen, and Janssen-Cilag. Dr. Sartor has served as a consultant or advisor to Novartis, Noria Therapeutics, Point Biopharma, Clarity, Lantheus, and Bayer. Dr. Heath has received honoraria from Bayer, Sanofi, and Seattle Genetics; has served as a consultant or advisory to Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, and Sanofi; has served on the speakers bureau of Sanofi; has received institutional research funding from Agensys, AIQ Solutions, Astellas Pharma, AstraZeneca, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Calibr, Caris Life Sciences, Celgene, Celldex, Champions Oncology, Corcept Therapeutics, Curemeta, Daiichi Sankyo Inc, Dendreon, eFFECTOR Therapeutics, Eisai, Esanik, Five Prime Therapeutics, Fortis, Genentech/Roche, GlaxoSmithKline, Ignyta, Infinity Pharmaceuticals, Inovio Pharmaceuticals, Janssen Research & Development, Medivation, Merck, Merck Sharp & Dohme, Millennium, Mirati Therapeutics, Modra Pharmaceuticals, Novartis, Oncolys BioPharma, Pellficure, Peloton Therapeutics, Pharmacyclics, Plexxikon, Seattle Genetics, Synta, Tokai Pharmaceuticals, and Zenith Epigenetics.
1. Merseburger A, Attard G, Boysen G, et al: A randomized, double-blind, placebo-controlled, phase 3b study of the efficacy and safety of continuing enzalutamide in chemotherapy-naive, metastatic castration-resistant prostate cancer patients treated with docetaxel plus prednisolone who have progressed on enzalutamide: PRESIDE. 2022 ASCO Genitourinary Cancers Symposium. Abstract 15. Presented February 17, 2022.