Lead-in ADT reduces grade ≥3 neutropenia incidence in metastatic hormone-sensitive prostate cancer patientsLead-in therapy may reduce severe low white blood cell counts

Med (New York, N.Y.) Published August 19, 2026 Study authors: Ni Xudong, Zhao Yufan, Wang Shanshan, Zhong Lei, Shi Xuedong, Li Xiaomeng, Ma Qi, Wu Yi, Ye Dingwei,… PubMed ↗ DOI ↗ Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

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Key Takeaway

Note that lead-in ADT is associated with lower rates of grade ≥3 neutropenia in patients receiving docetaxel for mHSPC.

This study utilized a post hoc analysis of the ARASENS cohort (n=847) and a real-world validation cohort (n=202) to evaluate the impact of lead-in androgen-deprivation therapy (ADT) on treatment toxicity in patients with metastatic hormone-sensitive prostate cancer (mHSPC). The primary outcome was the incidence of grade ≥3 neutropenia during the first cycle of docetaxel.

In the ARASENS cohort, lead-in ADT resulted in a lower incidence of grade ≥3 neutropenia compared to no lead-in ADT (11.36% vs. 17.17%; adjusted OR: 0.50; p = 0.0328; 95% CI: 0.26-0.95). The real-world validation cohort showed a similar trend with even lower odds in the lead-in group (11.03% vs. 37.88%; adjusted OR: 0.19; p < 0.0001; 95% CI: 0.09-0.42). No significant difference was reported for overall survival.

Safety data specifically focused on grade ≥3 neutropenia, which appeared lower in the lead-in group across both cohorts. However, as a post hoc analysis of a phase 3 trial, these results should be interpreted with caution regarding definitive clinical changes. The study provides evidence that lead-in ADT may contribute to improved prevention strategies for severe neutropenia during docetaxel administration.

How this fits prior evidence

How this fits prior evidence: This finding addresses a gap in managing treatment toxicity for metastatic hormone-sensitive prostate cancer. While previous coverage confirmed that darolutamide plus ADT and docetaxel reduces death risk 37% in metastatic hormone-sensitive prostate cancer, the current data specifically explores how lead-in ADT may mitigate grade ≥3 neutropenia during the initial docetaxel cycle.

Managing side effects is a major part of life with metastatic hormone-sensitive prostate cancer. One common and serious concern is neutropenia, which happens when the body has a dangerously low count of white blood cells. These are the cells that fight off infections.

A study looked at patients receiving triplet therapy to see if starting with a lead-in androgen-deprivation therapy (ADT) made a difference. The results showed that patients who received this lead-in treatment had lower rates of severe neutropenia during their first cycle of docetaxel compared to those who did not.

While the study was a post hoc analysis, meaning it looked back at existing data, real-world evidence supported these findings. While the lead-in therapy helped manage white blood cell counts, researchers did not find a difference in overall survival between the two groups. These results suggest that lead-in ADT could be a helpful tool for managing treatment safety.

What this means for you:

Lead-in hormone therapy may lower the risk of severe low white blood cell counts during chemotherapy.

Common questions

What is neutropenia and why does it matter?

Neutropenia happens when your body has a low number of white blood cells, which are the cells that fight infections. In this study, researchers looked at grade 3 or higher neutropenia, which is a more severe drop in these protective cells during chemotherapy.

How does lead-in therapy affect treatment safety?

The study found that patients who received lead-in androgen-deprivation therapy (ADT) had lower rates of severe neutropenia. In the real-world validation group, only 11.03% of those with lead-in ADT experienced it, compared to 37.88% of those without it.

Does this treatment change how long a patient lives?

While the lead-in therapy appeared to help manage white blood cell counts, the study did not find a significant difference in overall survival between the two groups. You should talk to your doctor about how these findings apply to your specific care plan.

Study Details

Study typePhase3

Sample sizen = 748

EvidenceLevel 2

PublishedJul 2026

PMID42127891

View Original Abstract ↓

BACKGROUND: Severe neutropenia (grade ≥3) is a major adverse event in patients with metastatic hormone-sensitive prostate cancer (mHSPC) receiving triplet therapy. The purpose of this study was to investigate the influence of lead-in androgen-deprivation therapy (ADT) on the incidence of grade ≥3 neutropenia. METHODS: This post hoc analysis of the ARASENS phase 3 trial compared patients with and without lead-in ADT. Inverse probability of treatment weighting (IPTW) balanced baseline characteristics. The primary endpoint was grade ≥3 neutropenia incidence. External validation utilized multicenter real-world data. FINDINGS: The ARASENS cohort included 847 patients (lead-in ADT, n = 748; no lead-in, n = 99). The lead-in-ADT group showed a lower incidence of grade ≥3 neutropenia during the first docetaxel cycle than the no-lead-in-ADT group (11.36% vs. 17.17%, p = 0.0328; adjusted odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.26-0.95). Overall survival showed no significant difference. Real-world validation (N = 202; lead-in ADT, n = 136; no lead-in ADT, n = 66) confirmed this lower incidence with lead-in ADT (11.03% vs. 37.88%, p < 0.0001; adjusted OR: 0.19, 95% CI: 0.09-0.42). CONCLUSIONS: Patients receiving lead-in ADT experienced a lower incidence of grade ≥3 neutropenia during the first docetaxel cycle than those not receiving lead-in ADT. This finding may contribute to improved prevention strategies for grade ≥3 neutropenia. FUNDING: This study was funded by the National Natural Science Foundation of China.

Lead-in ADT reduces grade ≥3 neutropenia incidence in metastatic hormone-sensitive prostate cancer patientsLead-in therapy may reduce severe low white blood cell counts

How this fits prior evidence

Common questions

Study Details

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Lead-in ADT reduces grade ≥3 neutropenia incidence in metastatic hormone-sensitive prostate cancer patientsLead-in therapy may reduce severe low white blood cell counts

How this fits prior evidence

Common questions

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