KEY TAKEAWAYS
- This phase 3 study compared enzalutamide plus ADT to placebo plus ADT regarding OS and other clinical outcomes based on varying baseline PSA levels in men with mHSPC.
- The study demonstrated enzalutamide’s clinical benefits for men with mHSPC, irrespective of their baseline PSA levels following ADT
In the ARCHES clinical trial (NCT02677896), the combination of enzalutamide and androgen deprivation therapy (ADT) demonstrated improved survival outcomes compared to the use of placebo alongside ADT in men diagnosed with metastatic hormone-sensitive prostate cancer (mHSPC). Despite existing recommendations in clinical guidelines, the adoption of treatment intensification strategies, such as enzalutamide combined with ADT, remains limited in real-world clinical settings.
This retrospective analysis aimed to assess the impact of enzalutamide plus ADT versus placebo plus ADT on overall survival (OS) and other clinical outcomes based on different baseline prostate-specific antigen (PSA) levels. Additionally, it investigated the factors influencing and consequences of achieving undetectable PSA levels in men with mHSPC.
In this study, men diagnosed with mHSPC were randomly assigned in a 1:1 ratio to receive either enzalutamide in combination with ADT or a placebo along with ADT. Analyses were carried out to evaluate the effectiveness of enzalutamide plus ADT in different subgroups categorized by their baseline PSA levels. Additional analyses were based on whether patients (pts) achieved undetectable PSA levels (<0.2 ng/mL) during the study treatment or not (≥0.2 ng/mL).
This analysis included men who had detectable PSA levels at the beginning of the study and had at least one PSA measurement after starting the treatment. A stepwise multivariate analysis was performed on variables derived from a univariate logistic regression model to identify factors associated with a decline to undetectable PSA.
The study revealed that the clinical benefits of enzalutamide combined with ADT versus placebo plus ADT were evident among men who had previously received ADT, irrespective of their initial PSA levels. Furthermore, among men who had detectable PSA levels at the start of the study and achieved undetectable PSA levels while on enzalutamide plus ADT, improved outcomes were observed. These benefits included a delay in radiographic progression, as determined by independent central review (hazard ratio [HR] 0.14; 95% CI 0.09, 0.23), and improved overall survival (HR 0.22; 95% CI 0.16, 0.30) compared to men who maintained detectable PSA levels after treatment. Predictors associated with reaching undetectable PSA levels while receiving enzalutamide plus ADT included baseline PSA levels (odds ratio [OR] 3.2 for below vs. above median [7.23 ng/mL], P<0.0001), baseline Eastern Cooperative Oncology Group (ECOG) performance status (OR 2.2 for 0 vs. ≥1, P=0.0034), and total Gleason score at initial diagnosis (OR 2.5 for <8 vs. ≥8, P=0.0011).
These findings highlight the clinical advantages of using enzalutamide in treating men with mHSPC, irrespective of their initial PSA levels following prior ADT. Among men with mHSPC treated with enzalutamide, those who achieved undetectable PSA levels exhibited better treatment outcomes than those with detectable PSA levels. It is worth noting that baseline PSA levels, ECOG performance status, and the total Gleason score at the time of initial diagnosis could serve as useful indicators for identifying individuals likely to attain undetectable PSA levels when undergoing enzalutamide combined with ADT.
Nurses play a vital role in patient education regarding the importance of treatment intensification for men diagnosed with mHSPC, regardless of their PSA levels before starting therapy. Even if PSA levels become undetectable due to prior ADT, nurses can reassure pts about the significance of achieving and maintaining undetectable PSA levels, as this can delay the progression of symptoms, metastasis, or mortality.
Nurses can actively support patients receiving optimal treatment by monitoring and managing treatment-related symptoms and side effects. They can assess baseline patient characteristics that may influence treatment response and overall quality of life, thus contributing to more personalized and effective care.
Source: https://ons.confex.com/ons/2023/meetingapp.cgi/Paper/13462
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02677896
Huebner, T., Williams, M., Shore, N., El-Chaar, N., Russell, D., Armstrong, A. P379 – Outcomes by Prostate-Specific Antigen Level in Metastatic Hormone-Sensitive Prostate Cancer Treated with Enzalutamide Plus Androgen Deprivation Therapy and Implications for Clinical Practice.
