Real-World Analysis Establishes OS Advantage With Apalutamide Plus ADT vs Darolutamide in mCSPC

Patients with metastatic castration-sensitive prostate cancer (mCSPC) treated in routine US clinical practice who initiated apalutamide (Erleada) plus androgen deprivation therapy (ADT) without docetaxel experienced a statistically significant overall survival (OS) advantage compared with those who initiated darolutamide (Nubeqa) plus ADT without docetaxel, according to findings from a retrospective, real-world, head-to-head analysis.

The analysis included patients who started treatment with apalutamide or darolutamide between August 2022 and June 2025 and applied propensity score matching to balance baseline clinical characteristics between cohorts.^1,2 With 24 months of follow-up, initiation of apalutamide (n = 1460) was associated with a 51% reduction in the risk of death compared with darolutamide (n = 287), underscoring a potential efficacy signal in a setting where prospective head-to-head data are lacking (HR, 0.49; 95% CI, 0.30-0.83; P = .007). The 24-month OS rate was 92% with apalutamide vs 86% with darolutamide.² These findings were presented at the 36th Annual International Prostate Cancer Update in February.

To contextualize these data, OncLive met with Mehmet Bilen, MD, director of the Genitourinary Medical Oncology Program at Winship Cancer Institute of Emory University in Atlanta, Georgia, to discuss the clinical implications of this real-world survival advantage, how they may inform treatment selection for patients who are not candidates for docetaxel, and what additional evidence is needed to further refine sequencing strategies in mCSPC.

OncLive: From a clinical perspective, what stands out most about the OS advantage with apalutamide plus ADT vs darolutamide plus ADT in this real-world head-to-head analysis?

Bilen: This is an important question that we try to answer every day in our clinical practice, like when we see a patient with mCSPC, because we have several good treatment options for our [patients], but unfortunately, we don’t have prospective head-to-head comparisons [between these options]. Because of that reason, this real-world analysis is going to be helpful for [oncologists to consider] before [choosing] treatment options.

This is a real-world, head-to-head comparison in a clinically commonly seen population, which is men with mCSPC. In this analysis, we compared ADT plus [apalutamide] without chemotherapy vs ADT plus [darolutamide] without chemotherapy. Overall, we saw a meaningful survival separation in this retrospective, real-world analysis. This is one of the first comparisons between those 2 agents. That’s why it is helpful and informative for [oncologists who manage] prostate cancer.

What key takeaways should oncologists draw from this real-world analysis comparing treatments for patients with mCSPC?

This is the first head-to-head analysis [comparing] OS outcomes for patients with mCSPC treated with [apalutamide] without chemotherapy vs [darolutamide] without chemotherapy. In this analysis, we did [a] 24-month follow-up, because that’s the available cutoff in this database. The study [results] demonstrated that patients initiating [apalutamide] without chemotherapy experienced a statistically significant 51% reduction in risk of death compared with those who initiated [darolutamide] without chemotherapy. This is an informative comparison, and it’s going to be helpful for all of us.

How should oncologists contextualize these real-world findings alongside evidence from randomized trials, such as the phase 3 TITAN trial (NCT02489318) of apalutamide plus ADT in mCSPC?

Overall, these real-world survival data are similar [to those seen in] the TITAN trial,…[which supported the FDA approval of] apalutamide for patients with mCSPC. In the TITAN trial, we saw OS and progression-free survival [PFS] improvement with ADT plus apalutamide vs ADT monotherapy. In the real-world data, we saw similar survival outcomes, and that supports our overall findings.

For patients who are not candidates for docetaxel or prefer to avoid chemotherapy, how might these findings inform selection among androgen receptor pathway inhibitors?

We have all these treatment options, and we know that ADT monotherapy is a suboptimal treatment for this patient population. We have to give at least a doublet. We have several doublet options, including apalutamide-, enzalutamide-, abiraterone-, and darolutamide-based combinations. We also have 2 triplet options: ADT plus darolutamide plus chemotherapy, and ADT plus abiraterone plus chemotherapy.

[Patients may have] a lot of chemotherapy anxiety and sometimes don’t want to receive chemotherapy for various reasons. Or sometimes, as oncologists, we think a doublet is the way to go, and the patient doesn’t need chemotherapy from the beginning. Then we need to make a decision among those 4 doublet options.

There are no head-to-head comparisons [between these regimens], and because of that, these real-world analyses can give us a hint at what the OS, PFS, [and] prostate-specific antigen reduction outcomes look like. Based on this [real-world analysis], we will make a more informed decision rather than a dealer’s choice.

How should oncologists balance the efficacy signals from these real-world survival data with safety and drug-drug interaction considerations?

These are helpful data, but they don’t mean that all patients need to change their treatment. If a patient is currently receiving one of these agents and tolerating it fine and it’s working, I don’t think we should recommend changing their treatment. But if a patient has early progression, or if this is a new patient about to start treatment, these data will be helpful. Sometimes we have anecdotal experience, but [in] the end, we need to have data to guide us. This [real-world analysis] will provide data for our day-to-day practice.

Looking ahead, what additional real-world or prospective data would help clarify optimal treatment sequencing and selection for patients with mCSPC?

We are doing a much better job with real-world analyses. The power of AI, databases, and FDA guidance on how to conduct a robust real-world analysis are important to set the framework. We want to make sure the data we create are reproducible, reliable, and informative. This study followed FDA guidance, which is important. Once we have that backbone, we have several questions we need to answer, and we are not going to have prospective trials for every question, especially in prostate cancer. [To identify] the ideal treatment sequence, we need [more] data, and real-world analyses can fill that gap.

The good thing is, we’re going to get more combinations and treatment options for patients, and we need to compare them side by side. For mCSPC, we have other agents coming, [such as] PSMA RLT [prostate-specific membrane antigen-direct radioligand therapy], biomarker-based treatment options, and PARP inhibitors. The menu is getting richer, which is a good problem, but at the end of the day, we need to compare [these treatment options] and understand what to choose. All [patients] will benefit from good real-world analyses.

References

1. Real-world head-to-head analysis shows 51% reduction in risk of death for patients with metastatic castration-sensitive prostate cancer treated with Erleada (apalutamide) versus darolutamide without docetaxel through 24 months. News release. Johnson & Johnson. February 2, 2026. Accessed February 2, 2026. https://www.jnj.com/media-center/press-releases/real-world-head-to-head-analysis-shows-51-reduction-in-risk-of-death-for-patients-with-metastatic-castration-sensitive-prostate-cancer-treated-with-erleada-apalutamide-versus-darolutamide-without-docetaxel-through-24-months
2. Lowentritt B, Bilen MA, Singhal M, et al. Real-world comparison of overall survival in patients with metastatic castration-sensitive prostate cancer initiating apalutamide without docetaxel versus darolutamide without docetaxel. Poster presented at: 36th International Prostate Cancer Update; February 1-4, 2026; Vail, CO.