Cancer-Control Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer With <i>BRCA</i> Gene or Tumor Suppressor Mutations Undergoing 177-Lutetium Prostate-Specific Membrane Antigen Radioligand Therapy.

Abstract

Several tumor gene mutations are known for metastatic castration-resistant prostate cancer (mCRPC). The individual response to 177-lutetium prostate specific membrane antigen radioligand therapy (Lu-PSMA) is under current investigation regarding the genomic profile of patients with mCRPC. We relied on the FRAMCAP database and compared progression-free survival (PFS) and overall survival (OS) rates of patients with mCRPC with breast cancer-related antigen (<i>BRCA</i>) or tumor suppressor gene mutations (<i>TP53</i>, <i>PTEN</i>, <i>RB1</i>). Specifically, subgroup analyses were performed for patients with Lu-PSMA-treated mCRPC. Of 194 patients with mCRPC, 22% was <i>BRCA1/2</i> versus 14% <i>PTEN/TP53/RB1</i> versus 63% without one of these mutations. Patients with no mutation harbored a significantly lower Gleason score of 8-10, relative to <i>BRCA</i> and <i>PTEN/TP53/RB1</i> patients. In PFS analyses of first-line mCRPC, no difference between all three groups was observed, whereas the median OS differed significantly with 46.3 versus 48.7 versus 95.4 months for <i>BRCA</i> versus <i>PTEN/TP53/RB1</i> versus no mutated patients (<i>P</i> < .05). In univariable Cox regression models, BRCA-mutated patients were at higher risk of death (hazard ratio, 2.57; <i>P</i> < .01), whereas <i>PTEN/TP53/RB1</i> patients were not (<i>P</i> = .4). Of 87 patients with Lu-PSMA-treated mCRPC, significant differences in PFS and OS were observed (both <i>P</i> ≤ .02). In univariable and multivariable Cox regression models, BRCA-mutated Lu-PSMA patients were at higher risk of death, whereas <i>PTEN/TP53/RB1</i> patients had similar outcomes as no mutated patients. In real-world setting, substantially lower OS in mCRPC is observed for <i>BRCA</i>- and <i>PTEN/TP53/RB1</i>-mutated patients, whereas no difference in first-line PFS could be computed. In Lu-PSMA-treated patients, worst outcomes were observed for <i>BRCA</i> patients.