In combination with androgen deprivation therapy (ADT), the novel androgen-receptor inhibitor rezvilutamide significantly improved radiographic progression-free survival (PFS) and overall survival (OS) compared with bicalutamide (Casodex) in patients with high-volume, metastatic, hormone-sensitive prostate cancer, the phase III CHART trial showed.
Among 654 mostly Asian patients, median radiographic PFS was not reached in the rezvilutamide group compared with 25.1 months in the bicalutamide group (HR 0.44, 95% CI 0.33-0.58, P<0.0001) at a median follow-up of 21.2 months, and overall survival was not reached in either group (HR 0.58, 95% CI 0.44-0.77, P=0.0001) at a median follow-up of 29.3 months, reported Dingwei Ye, MD, of Fudan University Shanghai Cancer Center in China, and colleagues.
The 2-year radiographic PFS rate was 72.3% in the rezvilutamide group and 50.0% in the bicalutamide group, while the 2-year OS rates were 81.6% and 70.3%, respectively, they noted in Lancet Oncology.
The benefits of rezvilutamide on radiographic PFS were observed in all subgroups, except for patients with visceral metastases and those not from China.
“Our findings further validate the clinical benefit of adding second-generation androgen-receptor axis inhibitors to the ADT backbone in patients with metastatic, hormone-sensitive prostate cancer,” Ye and colleagues wrote. “The observed clinical benefit and desirable safety profile in the two interim analyses support the use of rezvilutamide in combination with ADT as a standard-of-care for patients with high-volume metastatic, hormone-sensitive prostate cancer.”
In a commentary accompanying the study, Louise Kostos, MBBS, and Declan G. Murphy, MD, both of the Peter MacCallum Cancer Centre in Melbourne, Australia, noted that the OS benefit seen with rezvilutamide was “particularly impressive,” considering that the study’s control group of bicalutamide plus ADT was more active than the control groups in the ARCHES and TITAN trials — trials similar to CHART in that they compared an androgen-receptor inhibitor plus ADT to ADT alone.
“Rezvilutamide will be a welcome addition to the range of androgen-receptor inhibitors already available, and will — we hope — through a little healthy competition, overcome some of the barriers to real-world use of doublet therapy, such as cost and access,” Kostos and Murphy wrote.
They pointed out that previous studies have shown that prostate cancer in Asian and white men differs “epidemiologically and genomically, raising the question whether there might be a differential response to anti-androgen therapies, so it is interesting and reassuring to note that patients from China fared well in terms of progression-free survival and overall survival in the CHART trial.”
The randomized, open-label CHART trial was conducted at 72 hospitals in China, Poland, Czech Republic, and Bulgaria. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Previous chemotherapy or other localized treatment for prostate cancer were not allowed.
Ye and colleagues included 654 patients and randomly assigned them 1:1 to receive ADT plus either rezvilutamide 240 mg (n=326) or bicalutamide 50 mg (n=328) orally once daily from June 2018 to August 2020. Median age was 69, and 90% were Asian.
As for safety, the most common grade 3 or higher adverse events of any cause were hypertension (8% of patients in the rezvilutamide group vs 7% in the bicalutamide group), hypertriglyceridemia (7% vs 2%), increased weight (6% vs 4%), anemia (4% vs 5%), and hypokalemia (3% vs 1%). Serious adverse events were reported in 28% of the rezvilutamide group and 21% of the bicalutamide group. No treatment-related deaths occurred in patients in the rezvilutamide group, while one treatment-related death of unknown specific cause occurred in the bicalutamide group.
Ye and colleagues said that the major limitation to their study was that it excluded patients who had received chemotherapy. They suggested that since early use of docetaxel plus ADT is common as a standard-of-care therapy in patients with metastatic hormone-sensitive prostate cancer, “future studies are needed to investigate the clinical activity of rezvilutamide” in these patients who had been treated with docetaxel.
Disclosures
The study was funded by Jiangsu Hengrui Pharmaceuticals.
Ye reported grants from Merck Sharp & Dohme, Johnson & Johnson, and AstraZeneca, as well as membership on an independent data monitoring committee for Jiangsu Hengrui Pharmaceuticals.
Several co-authors reported they are employees of Jiangsu Hengrui Pharmaceuticals.
Kostos reported reimbursement for speaker duties from Bayer.
Murphy reported reimbursement for speaker duties and advisory board activity for Janssen, Bayer, Astellas, Ipsen, AstraZeneca, and Device Technologies.
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