Impact of lead-in ADT on grade ≥3 neutropenia in patients with metastatic hormone-sensitive prostate cancer treated with triplet therapy.

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.