Comparing OS and PFS Rates of Patients With mCRPC and BRCA, PTEN/TP53/RB1 Mutations

Metastatic castration-resistant prostate cancer (mCRPC) is commonly linked to several tumor gene mutations, such as mutations in homologous recombination repair (HRR) genes and breast cancer–related antigen (BRCA) genes.

A recent study analyzed and compared the progression-free survival (PFS) and overall survival (OS) rates among patients with mCRPC who harbored BRCA or tumor suppressor gene mutations (TP53, PTEN, RB1).

Because individual patient response to 177-lutetium prostate-specific membrane antigen radioligand therapy (Lu-PSMA) is under investigation in relation to genomic profiles of patients with mCRPC, subgroup analyses were also conducted for patients with Lu-PSMA–treated disease.

A total of 194 genomic profiles of patients with mCRPC were analyzed. BRCA 1/2 mutations were found in 22% of patients, and PTEN/TP53/RB1 mutations were found in 14% of patients. Neither mutation was seen in 63% of patients, who had significantly lower Gleason scores of 8 to 10, relative to patients with BRCA and PTEN/TP53/RB1 mutations.

In the PFS analyses of first-line treatment of mCRPC, no difference was observed between the three patient groups. However, the median OS differed significantly at 46.3, 48.7, and 95.4 months for patients with BRCA mutations, those with PTEN/TP53/RB1 mutations, and those without mutations, respectively (P<.05).

Univariable Cox regression models showed that patients with BRCA mutations had a higher risk of death (hazard ratio, 2.57; P<.01), while patients with PTEN/TP53/RB1 mutations did not (P=.4).

Among 87 patients with Lu-PSMA–treated mCRPC, significant differences in PFS and OS were seen (both P≤.02). In univariable and multivariable Cox regression models, patients with BRCA-mutated  mCRPC had a higher risk of death, whereas patients with mCRPC and PTEN/TP53/RB1 mutations had outcomes similar to those of patients with no mutations.

In a real-world setting, substantially lower OS was seen among patients with BRCA- and PTEN/TP53/RB1-mutated mCRPC, but no difference in PFS was determined. Worse outcomes were observed for patients with BRCA-mutated mCRPC who were treated with Lu-PSMA.