China ARCHES Study Meets Primary, Secondary End Points in Metastatic Prostate Cancer

Enzalutamide (Xtandi) plus androgen deprivation therapy (ADT) produced a statistically significant improvement in time to prostate-specific antigen (PSA) progression compared with ADT and placebo in men with metastatic hormone-sensitive prostate cancer (mHSPC), meeting the primary end point of the phase 3 China ARCHES study (NCT04076059).¹

Results also showed that the combination reduced the risk of radiographic progression and increased the rate of patients with undetectable PSA vs placebo plus ADT, meeting key secondary end points. The safety profile of the combination was similar to the known safety profile for the medication.

Detailed findings from the study will be submitted for publication in the near future. Investigators plan to share trial data with the China National Medical Products Administration (NMPA) to potentially support a regulatory filing.

“With the rising incidence of prostate cancer diagnoses among men in China, there is a need for new and effective treatment options,” Ahsan Arozullah, MD, MPH, senior vice president and head of Development Therapeutic Areas at Astellas, said in a press release. “As observed in our global phase 3 ARCHES study, and now reaffirmed with China ARCHES, [enzalutamide] significantly delays the time to disease progression in men with mHSPC and may provide an important treatment option for men in China if approved.”

In December 2019, the FDA approved enzalutamide for use in combination with ADT for the treatment of patients with mHSPC.² The decision was based on earlier findings from the phase 3 ARCHES trial (NCT02677896), in which 1150 patients were randomly assigned to receive ADT plus 160 mg of enzalutamide daily or placebo. Patients were stratified by disease volume and prior docetaxel use.

Primary results demonstrated that the addition of enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS), as well as key secondary end points, vs placebo/ADT in this patient population.³ A long-term OS benefit was also reported in a subsequent analysis.⁴

Moreover, findings from a post hoc analysis presented at the 2022 AUA Annual Meeting showed that the combination provided a benefit in OS, rPFS, undetectable PSA rates, objective response rates (ORRs), and other end points vs placebo/ADT. Patients derived benefit regardless of whether or not they received prior local therapy.⁵

China ARCHES is a multicenter, phase 3, randomized, double-blind, placebo-controlled trial that enrolled 180 Chinese patients with mHSPC across 30 sites in mainland China. Patients in the trial were randomly assigned to 160 mg of enzalutamide daily or placebo, continued on a luteinizing hormone-releasing hormone agonist or antagonist, or had a history of bilateral orchiectomy.

The primary end point of the trial was time to PSA progression, defined as a 25% or greater increase and an absolute increase of at least 2 ng/mL above the nadir, which was confirmed by a second consecutive value at least 3 weeks later. Secondary end points included rPFS, time to first symptomatic skeletal event, time to castration resistance, PSA response of 50% or greater, PSA response of 90% or greater, and time to initiation of new antineoplastic therapy. Additional secondary end points included PSA undetectable rate, which will be defined as the percentage of patients with detectable PSA at baseline measuring at least 0.2 ng/mL, which becomes undetectable at a level below 0.2 ng/mL during study treatment, and objective response rate.

“While past global studies have supported the use of [enzalutamide] plus ADT in men with mHSPC, it is encouraging to see these results replicated for patients in mainland China,” Zhou Fangjian, MD, head of the Urology Department at Sun Yat-sen University Cancer Center, Sun Yat-sen University, stated.

“As an existing standard of care for Chinese men with castration-resistant prostate cancer, [enzalutamide] has the potential to help men earlier in their treatment journey—before their disease stops responding to therapies that lower testosterone,” Professor Dingwei Ye, MD, PhD, vice president of the Fudan University Shanghai Cancer Center and director of the Multi-disciplinary Team for GU Cancer, concluded.

References

1. Astellas announces phase 3 China ARCHES study of XTANDI® meets primary endpoint. News release. Astellas Pharma. March 13, 2023. Accessed March 14, 2023. https://newsroom.astellas.us/2023-03-13-Astellas-Announces-Phase-3-China-ARCHES-Study-of-XTANDI-R-Meets-Primary-Endpoint
2. Xtandi (Enzalutamide) approved by US FDA for the treatment of metastatic castration-sensitive prostate cancer. News release. Pfizer. December 16, 2019. Accessed March 14, 2023. https://www.pfizer.com/news/press-release/press-release-detail/xtandi_enzalutamide_approved_by_u_s_fda_for_the_treatment_of_metastatic_castration_sensitive_prostate_cancer
3. Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al. ARCHES: a randomized, phase iii study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2019;37(32):2974-2986. doi:10.1200/JCO.19.00799.
4. Armstrong AJ et al. Improved survival with enzalutamide in patients with metastatic hormone-sensitive prostate cancer. J Clin Oncol. Published online April 14, 2022. doi:10.1200/JCO.22.00193
5. Shore ND, Iguchi T, Villers A, et al. Overall survival in patients with metastatic hormone-sensitive prostate cancer treated with enzalutamide or placebo plus androgen deprivation therapy who had prior local therapy: post hoc analysis of the phase 3 ARCHES trial. Presented at: 2022 AUA Annual Meeting, May 13-18, 2022; New Orleans, LA. Abstract 22-5476.