PSA kinetics can be used to monitor nmCRPC prognosis: PSA deep remission is associated with long-term clinical benefit

‍‍SPARTAN post hoc exploratory analysis evaluated the efficacy prediction and prognostic value of PSA kinetics in nmCRPC patients.
The results were recently published in the journal EUROPEAN UROLOGY
.

nmCRPC patients with shorter background prostate-specific antigen (PSA) doubling time (PDADT) have an increased risk of distant metastasis and worse clinical outcomes compared with longer PSADT
.

Previous results from SPARTAN showed that apalutamide + androgen deprivation therapy (ADT) improved metastasis-free survival (MFS), delayed PSA progression, and significantly improved overall survival (OS) in CRPC patients with PSADT ≤10 nm
.

The basal/luminal subtype based on the Decipher test is considered to be aggressive prostate cancer, using Decipher genotyping (GC) for molecular classification, patients with high GC score (high risk) have poor prognosis, Luminal A and basal subtypes are Considered intolerance to ADT
.

In the SPARTAN study, high-risk groups and ADT-intolerant basal subtypes accounted for 50% and 65%, respectively.
Apalutamide can improve the prognosis of all subgroups, including high-risk patients, filling the treatment needs of ADT-intolerant basal subtypes.

.

However, patients with luminal subtype have a greater survival benefit
.

However, PSA kinetics in patients with each molecular stratification in the SPARTAN study still needs to be further evaluated, and PSA kinetics have not been extensively studied in nmCRPC
.

In this SPARTAN post hoc analysis, we assessed the efficacy predictive and prognostic value of apalutamide PSA kinetics
.

We also assessed the correlation of Decipher test and molecular subtyping results with PSA kinetics and the association of PSA remission with patient outcomes in nmCRPC patients receiving apalutamide
.

Methods SPARTAN is a phase III randomized, double-blind, controlled study in patients with high-risk nmCRPC (PSADT ≤ 10 months) who were randomly assigned in a 2:1 ratio to receive apalutamide (240 mg/d, n=806) or placebo.
(n=401) + ongoing ADT
.

This post hoc analysis assessed the correlations between PSA kinetics and MFS, OS, time to PSA progression, and molecular subtypes using landmark analysis and the Kaplan-Meier method
.

Results A total of 1207 patients were included, 806 in the apalutamide group and 401 in the placebo group (Figure 1)
.

The patient characteristics of the two groups were balanced and comparable
.

Figure 1.
SPARTAN study design.
Apalutamide improves PSA kinetics.
Median PSA at baseline was similar between the two treatment groups (Table 1)
.

At 3 months of treatment, compared with baseline, most patients in the apalutamide group had lower PSA levels (Figure 2A), while placebo-treated patients had higher PSA levels (Figure 2B)
.

Figure 2 PSA levels of patients
.

Compared with baseline, patients in the apalutamide and placebo groups had the greatest change in PSA levels at 6 months of treatment
.

Table 1 PSA kinetics in patients enrolled in the SPARTAN study 90% of patients treated with apalutamide achieved a study-defined optimal PSA reduction of ≥50% at 6 months of treatment (Table 1); median time was 1.
0 month
.

After 6 months of apalutamide treatment, 57% and 32% of patients achieved deep PSA remission with a PSA reduction of ≥90% or ≤0.
2 ng/ml, respectively, for a median of 1.
9 months and 2.
8 months, respectively
.

Only 1.
5% of patients in the placebo group had a ≥50% reduction in PSA at 6 months
.

Patients treated with apalutamide rapidly achieved optimal PSA remission within 3 months
.

Optimal PSA reduction ≥50% and deep PSA ≥90% reduction or PSA ≤0.
2 ng/ml were observed early in most patients
.

A small proportion of patients achieved ≥ 50% PSA reduction and deep PSA reduction after 12 months of apalutamide treatment
.

In contrast, 98% of patients in the placebo group had little or no reduction in PSA (<50%)
.

Baseline characteristics of the SPARTAN biomarker population (n = 233) in both treatment groups for PSA remission by molecular subtype were similar to the overall population
.

Of these, the majority of patients (apalutamide [75%], placebo [72%]) had a PSADT of ≤6 months
.

Patients in the apalutamide group were classified as GC high risk, GC low risk, basal subtype, and luminal subtype
.

PSA kinetics were similar across subgroups (Table 2)
.

Table 2 PSA kinetics of molecular subtypes in the apalutamide group in the SPARTAN study Correlation of PSA remission with outcomes in patients treated with apalutamide PSA reduction ≥50% and deep PSA reduction ≥90% at 6 months of treatment Or PSA ≤0.
2 ng/ml was associated with shorter time to PSA progression (HR 0.
21, 0.
25, and 0.
13; all P<0.
001) and improved OS (HR=0.
5, P=0.
008; HR=0.
45, P<01; HR=0.
26, P<0.
001 (Table 3, Figure 3 AC)
.

Figure 3 Clinical results of patients with reduced PSA treated with apalutamide for 6 months Prognostic relevance
.

At 6 months of treatment, PSA reduction ≥50%, deep PSA reduction ≥90%, or PSA ≤0.
2 ng/ml were also significantly associated with improved MFS (Table 3 )
.

Median time to PSA progression and OS were significantly improved in patients with a PSA reduction of 50%-<90% compared to patients with a
PSA
reduction of <50% and a PSA reduction of ≥ Median time to PSA progression and OS were significantly improved in 90% of patients (Figure 3D and F)
.
Conclusions
Apalutamide+ADT treatment of high-risk nmCRPC patients produced rapid, deep, and durable PSA remissions regardless of molecular subgroup
.

Moreover, early PSA remission with apalutamide is associated with clinical benefit, and monitoring PSA has prognostic value .