Apalutamide Demonstrates Efficacy After Prostate-Directed Local Therapy for nmCRPC

Apalutamide (Erleada; Janssen Biotech) following prostate-directed local therapy (LT) demonstrated clinically significant and more favorable treatment effect in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), according to data from the SPARTAN trial (NCT01946204). The post ad hoc analysis of the trial data offers hypothesis generating evidence of the efficacy of this treatment, potentially leading to continued investigations and improved therapeutic options for patients.¹

At the median follow-up of 52 months, patients with prior LT receiving apalutamide experienced greater benefits than those without. Image Credit: © Phushutter - stock.adobe.com

According to the American Cancer Society, almost 300,000 men in the United States will be diagnosed with prostate cancer in 2024 and about 1 in 44 individuals die from the disease. Rates have bee declining over the decades, with a notable decrease by about 50% between 1993 and 2013. This is largely due to increased early detection and improved screening that allow for clinicians to intervene before the cancer progresses to advanced stages. Despite this noticeable decline, there are still patients who experience worse disease and poorer prognoses.^2,3

There are various treatment options available including hormone therapy, chemotherapy, novel drug therapies, and castration. There are 2 types of castration: medical, which involves use of agents to lower testosterone; and surgical, which is the partial or fill removal of the testes. NmCRPC refers to the progression of prostate cancer in a castration environment with very low serum testosterone concentration.⁴

Apalutamide is an androgen receptor inhibitor that block the effects of androgen, a male reproductive hormone, that stops the growth and spread of cancer cells. It is a type of hormone therapy indicated for nmCRPC. In the post ad hoc analysis of the multicenter, randomized, double-blind, placebo-controlled, phase 3 SPARTAN trial, patients taking apalutamide after LT experienced a differential treatment effect compared with those who did not receive LT.⁵

The researchers used cox proportional hazard regression models for overall survival (OS) and metastasis-free survival (MFS), which included prior LT, treatment group, and an interaction term, in 1179 patients with nmCRPC. Of the participants, 795 received prior LT and 384 did not.⁶

At the median follow-up of 52 months, patients with prior LT receiving apalutamide experienced greater benefits (adjusted HR, 0.22 [95% CI, 0.17-0.27]) than those without (adjusted HR, 0.35 [95% CI, 0.25-0.51]). There was also an observed treatment differential effect. Regarding OS, the cohort of patients who had a prior LT saw an improvement in OS, with an adjusted hazard ratio (HR) of 0.72 (confidence interval [CI] of 0.57–0.92). Patients without prior LT experienced no significant difference in OS (95% CI, 0.64–1.31), indicating a less clear effect.⁶

These initial findings show promise for research into use of apalutamide after LT for patients with nmCRPC. However, these data are part of a post ad hoc analysis, meaning further studies are needed to validate the results.

REFERENCES

1. A study of apalutamide (arn-509) in men with non-metastatic castration-resistant prostate cancer (spartan). ClinicalTrials.gov Identifier: NCT01946204. Updated October 21, 2024. Accessed October 28, 2024. https://clinicaltrials.gov/study/NCT01946204

2. Key statistics for prostate cancer. American Cancer Society. January 19, 2024. Accessed October 28, 2024. https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html

3. Prostate cancer. Mayo Clinic. June 14, 2024. Accessed October 28, 2024. https://www.mayoclinic.org/diseases-conditions/prostate-cancer/symptoms-causes/syc-20353087

4. Morote J, Aguilar A, Planas J, et al. Definition of castrate resistant prostate cancer: new insights. National Library of Medicine. March 17, 2022. Accessed October 28, 2024. https://pmc.ncbi.nlm.nih.gov/articles/PMC8945091/

5. Apalutamide. MedlinePlus. October 20, 2024. Accessed October 28, 2024. https://medlineplus.gov/druginfo/meds/a618018.html

6. Roy S, Malone S, Wing K, et al. Prior local therapy and first-line apalutamide in patients with nonmetastatic castration-resistant prostate cancer a secondary analysis of the spartan randomized clinical trial. JAMA Netw Open. October 15, 2024. doi:10.1001/jamanetworkopen.2024.39434