Home›Urology› Enzalutamide added to ADT improves survival in APIC-negative metastatic hormone-sensitive prostate cancer
Enzalutamide added to ADT improves survival in APIC-negative metastatic hormone-sensitive prostate cancerTrial shows enzalutamide helps specific patients with prostate cancer
Clinical cancer research : an official journal of the American Association for Cancer ResearchPublished October 15, 2026Study authors: Medina Sebastian, Tokuyama Naoto, Putcha Vaishnavi, Pathak Tilak, Fu Pingfu, Thomas Hayley, Subhash …PubMed ↗NCT02446405 ↗DOI ↗Editorial oversight: Dr. Lars van Dijk, PhD · Surgical, Procedural & Diagnostic
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Key Takeaway
Note that enzalutamide plus ADT significantly improves survival in patients with APIC-negative metastatic prostate cancer.
This randomized controlled trial included 492 patients with metastatic hormone-sensitive prostate cancer (mHSPC) to evaluate the efficacy of enzalutamide combined with androgen deprivation therapy (ADT) compared to a nonsteroidal antiandrogen (NSAA). The study specifically focused on the role of the APIC biomarker in predicting treatment response. The primary outcome measured was overall survival (OS) over a follow-up period of 68.8 months.
The study design involved comparing enzalutamide plus ADT against an NSAA. The analysis sought to determine if the presence or absence of APIC-positive disease influenced the survival outcomes of these two treatment regimens. This biomarker analysis was conducted within the larger ENZAMET trial framework.
In patients with APIC-negative disease, the addition of enzalutamide to ADT showed a significant improvement in overall survival compared to NSAA. The hazard ratio (HR) for this group was 0.50 (95% CI, 0.35-0.73). Specifically, the 60-month OS rate was 76.5% for the enzalutamide group compared to 58.3% for the NSAA group. In contrast, for patients with APIC-positive disease, there was limited evidence of benefit for enzalutamide, with an HR of 1.04 (95% CI, 0.67-1.62) and 60-month OS rates of 55.6% versus 58.8%.
Statistical analysis confirmed a significant treatment-by-APIC interaction for OS (P = 0.014), indicating that the APIC biomarker significantly modified the observed benefit of enzalutamide. Subgroup analyses further supported this; in low-volume disease (APIC-negative), enzalutamide improved survival with an HR of 0.31 (95% CI, 0.16-0.62). In low-volume disease (APIC-positive), no significant improvement was observed with enzalutamide (HR, 1.04; 95% CI, 0.53-2.06; interaction P = 0.015).
Additional data regarding treatment history also influenced outcomes. In non-docetaxel-treated participants with APIC-negative disease, enzalutamide showed a greater benefit with an HR of 0.40 and 60-month OS of 82% versus 61.0%. In non-docetaxel-treated participants with APIC-positive disease, the benefit was less pronounced, with an HR of 0.79 and 60-month OS of 62.8% versus 57.6%.
Safety and tolerability data, including specific adverse event rates or discontinuation rates, were not reported. The study's primary limitation is that it is an analysis of a biomarker within a larger trial, which may impact the generalizability of the specific biomarker findings.
These results suggest that the presence of APIC-negative disease identifies a specific patient population that experiences a major improvement in OS when receiving enzalutamide plus ADT compared to NSAA. This finding highlights the potential of APIC as a predictive biomarker in mHSPC. However, because this is a biomarker analysis of a randomized trial, the evidence is not yet sufficient to establish definitive clinical guidelines. Questions remain regarding the clinical utility of the APIC test in routine practice and the long-term durability of the observed survival benefits in the APIC-negative cohort.
How this fits prior evidence
How this fits prior evidence: This finding addresses a gap in precision oncology and biomarker-driven strategies for prostate cancer. It builds upon previously reported evidence that biomarker-driven strategies and genomic classifiers may improve risk stratification in prostate cancer by identifying specific patient populations, such as those with APIC-negative disease, who derive significant benefit from enzalutamide.
Managing metastatic hormone-sensitive prostate cancer (mHSPC) is a significant challenge for many patients. Because every patient's cancer behaves differently, doctors are always looking for ways to better predict which treatments will work best for specific individuals. This research focuses on finding a way to personalize treatment plans to improve long-term survival.
Researchers conducted a randomized controlled trial to compare two different treatment paths. They looked at 492 patients with metastatic hormone-sensitive prostate cancer. One group received a combination of androgen deprivation therapy (ADT) and a drug called enzalutamide. The other group received ADT combined with a different type of medication called a nonsteroidal antiandrogen (NSAA). The study followed these patients for nearly six years to see how their health progressed over time.
The study focused on a specific marker called APIC. The results showed a significant difference based on this marker. For patients whose cancer was identified as APIC-negative, those who received enzalutamide showed a notable improvement in overall survival compared to those who received the NSAA. In this specific group, the 60-month survival rate was 76.5% for those on enzalutamide, compared to 58.3% for those on the other medication. However, for patients with APIC-positive disease, the study found limited evidence that enzalutamide provided a significant benefit over the other treatment.
While the study did not report specific safety concerns or side effects, it is important to remember that this was a biomarker analysis within a larger trial. This means the results are based on looking at specific data points to see how they correlate with treatment success. Because this is a single study focusing on a specific biomarker, the results should be viewed as a piece of a larger puzzle rather than a definitive rule for all patients.
For patients right now, these findings suggest that the APIC marker could eventually help doctors make more informed decisions about which medication to choose. It highlights that not all prostate cancer is the same, and certain markers might help predict who will do better on specific drugs. Patients should speak with their oncology team to discuss how these types of markers might influence their specific treatment plan.
What this means for you:
A specific biomarker may help identify which prostate cancer patients are more likely to benefit from enzalutamide.
More on metastatic hormone-sensitive prostate cancer
PURPOSE: The ENZAMET trial established that enzalutamide added to androgen deprivation therapy (ADT) improves overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC), but treatment response is heterogeneous. We tested whether the artificial intelligence pathology image classifier (APIC), previously developed and locked in CHAARTED, predicts OS benefit from enzalutamide in ENZAMET.
EXPERIMENTAL DESIGN: This biomarker study applied APIC to digitized hematoxylin and eosin specimens from ENZAMET [Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) 1304, NCT02446405]. ENZAMET randomized participants with mHSPC to ADT plus enzalutamide or nonsteroidal antiandrogen (NSAA), with early concurrent docetaxel permitted. APIC was applied without modification or retraining. The prespecified primary analysis evaluated the treatment-by-APIC interaction for OS using Cox models adjusted for standard clinical factors. Prespecified sensitivity analysis excluded participants receiving early concurrent docetaxel.
RESULTS: Among 1,125 participants, 492 with digitized tissue (median follow-up, 68.8 months) were eligible. APIC classified 316 (64%) as APIC negative and 176 (36%) as APIC positive. APIC significantly modified enzalutamide benefit (interaction P = 0.014). APIC-negative disease showed improved survival with enzalutamide versus NSAA [HR, 0.50; 95% confidence interval (CI), 0.35-0.73; 60-month OS, 76.5% vs. 58.3%], whereas APIC-positive disease showed limited evidence of benefit (HR, 1.04; 95% CI, 0.67-1.62; 60-month OS, 55.6% vs. 58.8%). In low-volume disease, enzalutamide improved survival in APIC-negative (HR, 0.31; 95% CI, 0.16-0.62) but not APIC-positive disease (HR, 1.04; 95% CI, 0.53-2.06; interaction P = 0.015). For non-docetaxel-treated participants, enzalutamide benefit was greater in APIC-negative (HR, 0.40; 60-month OS 82% vs. 61.0%) than in APIC-positive participants (HR, 0.79; 60-month OS, 62.8% vs. 57.6%).
CONCLUSIONS: The presence of APIC-negative disease identified participants with a major improvement in OS with the addition of enzalutamide to ADT compared with the addition of NSAA.
