Biomarkers in Nonmetastatic Castrate-Resistant Prostate Cancer: A Step in the Right Direction
Menée à partir d'échantillons tumoraux issus de patients atteints d'un cancer de la prostate non métastatique résistant à la castration et inclus dans un essai de phase III évaluant l'ajout de l'apalutamide à un traitement anti-androgénique (âge médian : 73 ans), cette étude évalue l'association entre un score génomique, estimant le risque de développer des métastases, le sous-type moléculaire de la tumeur (basal, luminal, luminal-basal) et la réponse thérapeutique
Three recent landmark trials have redefined the standard of care for patients with nonmetastatic, castrate-resistant prostate cancer (nmCRPC). These trials demonstrate that for men with nmCRPC and a prostate-specific antigen doubling time of 10 months or fewer, the addition of a second-generation androgen signaling inhibitor (ASI) to androgen deprivation therapy (ADT) prolongs not only metastasis-free survival (MFS) but also overall survival.Despite these advances, biomarkers for prognosticating the outcomes of men with nmCRPC, as well as predicting response to second-generation ASI, remain lacking. In this issue of JAMA Oncology, Feng and colleagues report on a secondary analysis of gene expression data from patients in the SPARTAN trial, which randomized 1207 men with nmCRPC to ADT plus apalutamide or placebo and demonstrated significant improvements with apalutamide in both MFS (median, 40.5 vs 16.2 months; hazard ratio, 0.28; 95% CI, 0.23-0.35; P < .001) and overall survival (median, 73.9 vs 59.9 months; hazard ratio, 0.78; 95% CI, 0.64-0.06, P < .001). Of the overall cohort, 233 patients underwent successful gene expression profiling from the initial diagnostic biopsy or radical prostatectomy specimen with the Decipher test. The gene expression data were then used to generate the Decipher genomic classifier (GC) score and the luminal vs basal molecular subtype using an established algorithm. Feng and colleagues found that (1) patients with nmCRPC appear to be modestly enriched for GC high-risk disease and highly enriched for the basal subtype compared with a large registry of patients with localized disease who have undergone the Decipher test; (2) apalutamide was significantly associated with improved MFS for patients at both high risk and low risk for GC, as well as for both luminal and basal subtypes; (3) patients at high risk for GC had worse MFS when treated with ADT alone, but in the presence of apalutamide, MFS for patients at high risk and low risk for GC did not significantly differ; and (4) patients with luminal and basal subtypes did not have significantly different MFS when treated with ADT alone, but in the presence of apalutamide, MFS favored patients with luminal subtypes.
JAMA Oncology , éditorial en libre accès, 2020