US Food and Drug Administration Approval Summary: Talazoparib in Combination With Enzalutamide for Treatment of Patients With Homologous Recombination Repair Gene-Mutated Metastatic Castration-Resistant Prostate Cancer.
J Clin Oncol
; 42(15): 1851-1860, 2024 May 20.
Article
in En
| MEDLINE
| ID: mdl-38452327
ABSTRACT
PURPOSE:
The US Food and Drug Administration (FDA) approved talazoparib with enzalutamide for first-line treatment of patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC). PATIENTS ANDMETHODS:
The approval was based on the HRR gene-mutated (HRRm) population of TALAPRO-2, a randomized, double-blind trial that randomly assigned 1,035 patients with mCRPC to receive enzalutamide with either talazoparib or placebo. Two cohorts enrolled sequentially an all-comer population (Cohort 1), followed by an HRRm-only population (Cohort 2). The independent primary end points were radiographic progression-free survival (rPFS) per blinded independent central review (BICR) in Cohort 1 (all-comers) and in the combined HRRm population (all HRRm patients from Cohorts 1 and 2). Overall survival (OS) was a key secondary end point.RESULTS:
A statistically significant improvement in rPFS by BICR was demonstrated in both the all-comers cohort and the combined HRRm population, with hazard ratio (HR) of 0.63 (95% CI, 0.51 to 0.78; P < .0001) and 0.45 (95% CI, 0.33 to 0.61; P < .0001), respectively. In an exploratory analysis of the 155 patients with BRCA-mutated (BRCAm) mCRPC, rPFS HR was 0.20 (95% CI, 0.11 to 0.36). In the non-HRRm/unknown stratum of Cohort 1 (n = 636), the rPFS HR was 0.70 (95% CI, 0.54 to 0.89). OS was immature.CONCLUSION:
Despite a statistically significant rPFS improvement in the all-comer cohort, FDA did not consider the magnitude of rPFS clinically meaningful in the context of the broad indication, combination treatment, and safety profile. Approval was therefore limited to patients with HRRm mCRPC, for whom there was a statistically significant and clinically meaningful improvement in rPFS and favorable OS results. This represents the first approval for the first-line treatment of patients with HRRm mCRPC.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phenylthiohydantoin
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Phthalazines
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United States Food and Drug Administration
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Benzamides
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Antineoplastic Combined Chemotherapy Protocols
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Drug Approval
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Recombinational DNA Repair
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Prostatic Neoplasms, Castration-Resistant
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Mutation
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Nitriles
Limits:
Aged
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Aged80
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Humans
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Male
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Middle aged
Country/Region as subject:
America do norte
Language:
En
Journal:
J Clin Oncol
/
J. clin. oncol
/
Journal of clinical oncology
Year:
2024
Document type:
Article
Country of publication: