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Published on: March 6, 2018
The Impact of Early Modification of Upfront Androgen Receptor Signaling Inhibitors on Survival Outcomes in Metastatic
Shintaro Narita1, Takafumi Yanagisawa2, Shingo Hatakeyama3
1Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
Background:
This study evaluates the impact of early modification of upfront androgen receptor signaling inhibitors (ARSI) on outcomes among patients with metastatic hormone-sensitive prostate cancer (mHSPC).
Methods:
This retrospective, multicenter cohort study included 590 patients with mHSPC who received upfront ARSI combined with androgen deprivation therapy. All had a follow-up duration of ≥ 6 months. The impact of early modification of ARSI without progression on survival outcomes was analyzed. The inverse probability of treatment weighting (IPTW) was applied to adjust for confounding factors associated with survival outcomes, comparing patients who did and did not discontinue ARSI early.
Results:
Upfront abiraterone acetate, apalutamide, and enzalutamide were used in 50.8%, 28.1%, and 21.0% of patients, respectively. The rates of withdrawal of the upfront ARSI and initial dose reduction were 21.2% and 6.1%, respectively. The highest withdrawal rate (33.1%) was with apalutamide, mainly due to adverse events (89.1%). Apalutamide use (odds ratio [OR] 2.39, 95% CI: 1.50-3.80) and a low-risk CHAARTED status (OR 1.84, 95% CI: 1.08-3.14) were identified as independent risk factors for early ARSI withdrawal. IPTW analysis revealed early ARSI withdrawal (within 6 months) significantly correlated with poor castration-resistant prostate cancer-free survival (CRPC-FS) (p = 0.004) and second progression-free survival (PFS2) (p = 0.035). However, it had no significant relationship with overall survival (p = 0.280).
Conclusions:
Early withdrawal of initial upfront ARSI was associated with poor CRPC-FS and PFS2 among mHSPC patients. Maximizing the effectiveness of first-line treatment requires optimal management of ARSI therapy.
Trial Registration:
jRCTs021180021.
Insights
Early withdrawal of androgen receptor signaling inhibitors (ARSI) in metastatic hormone-sensitive prostate cancer (mHSPC) patients is linked to worse progression-free survival. Optimal management of ARSI therapy is crucial for maximizing treatment effectiveness.
Area of Science:
- Oncology
- Pharmacology
Background:
- Metastatic hormone-sensitive prostate cancer (mHSPC) management involves androgen receptor signaling inhibitors (ARSI).
- Early modification or withdrawal of upfront ARSI may impact patient outcomes.
- Understanding these impacts is crucial for optimizing treatment strategies.
Purpose of the Study:
- To evaluate the effect of early ARSI modification on survival outcomes in mHSPC patients.
- To identify risk factors associated with early ARSI withdrawal.
- To inform clinical practice regarding ARSI management in mHSPC.
Main Methods:
- Retrospective, multicenter cohort study of 590 mHSPC patients.
- Analysis of early ARSI modification (withdrawal or dose reduction) without progression.
- Inverse probability of treatment weighting (IPTW) used to adjust for confounders.
Main Results:
- Early ARSI withdrawal (within 6 months) was associated with significantly poorer castration-resistant prostate cancer-free survival (CRPC-FS) and second progression-free survival (PFS2).
- Apalutamide use and low-risk CHAARTED status were independent risk factors for early ARSI withdrawal.
- No significant association was found between early ARSI withdrawal and overall survival.
Conclusions:
- Early withdrawal of upfront ARSI in mHSPC patients correlates with inferior CRPC-FS and PFS2.
- Effective first-line treatment necessitates optimal management and adherence to ARSI therapy.
- Further research may explore strategies to mitigate early ARSI discontinuation.
