DNA damaging therapies in patients (pts) with prostate cancer (PC) and pathogenic alterations in homologous recombination repair (HRR) genes
Recommended Citation
Graham L, Green E, Park JJ, Kellezi O, Hwang C, Barata PC, Bilen MA, Kilari D, Clingerman M, Tripathi A, Labriola M, Rothstein S, Garje R, Koshkin VS, Patel VG, Dorff TB, Armstrong AJ, McKay RR, Alva AS, Schweizer MT. DNA damaging therapies in patients (pts) with prostate cancer (PC) and pathogenic alterations in homologous recombination repair (HRR) genes. J Clin Oncol 2022; 40(6 SUPPL).
Document Type
Conference Proceeding
Publication Date
2-16-2022
Publication Title
J Clin Oncol
Keywords
ATM protein, BRCA1 associated ring domain protein 1, BRCA1 protein, BRCA2 protein, checkpoint kinase 1, checkpoint kinase 2, endogenous compound, Fanconi anemia group A protein, Fanconi anemia group L protein, nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor, partner and localizer of BRCA2, platinum, Rad51 protein, Rad54 protein, adult, cancer patient, cancer survival, chemotherapy, clinical evaluation, cohort analysis, conference abstract, controlled study, drug combination, drug therapy, gene mutation, homology directed repair, human, major clinical study, male, metastasis, outcome assessment, overall survival, progression free survival, prostate cancer, retrospective study, sample size
Abstract
Background: Pathogenic HRR gene mutations may confer sensitivity to PARP inhibitors (PARPi) and/or platinum chemotherapy (chemo). While pts harboring mutations in BRCA1/2 appear to benefit from these DNA damaging therapeutics, outcomes data for those with non-BRCA1/2 mutations are less robust. We evaluated outcomes in men with HRR gene-mutated PC who received treatment with PARPi and/or platinum-based chemo stratified by type of HRR alteration. Methods: Retrospective data from the PROMISE Consortium was utilized (PMID: 34363009). PC pts with pathogenic HRR mutations who received PARPi and/or platinum-based chemo were included. Differences in PSA progression-free survival (PFS), clinical/radiographic PFS (rPFS), and overall survival (OS) between those with BRCA1/2 mutations (Cohort A) and those with mutations in HRR genes that do not directly interact with the BRCA complex (Cohort B: ATM, CDK12, CHEK1, CHEK2, FANCL) were evaluated. We also evaluated outcomes in pts with HRR gene mutations known to interact with the BRCA complex aside from BRCA1/2 (Cohort C: RAD51B/C/D, RAD54L2, BARD1, GEN1, PALB2, FANCA, BRIP1). Results: Of 361 pts identified with HRR gene alterations, 89 received PARPi and 70 received platinum-based chemo. Prior therapy and metastatic disease sites were similar between cohorts. PSA PFS, rPFS, and OS were significantly improved in Cohort A vs. Cohort B with PARPi but not platinum-based chemo (Table). Sample size in cohort C was too small to allow for statistical comparison, although PSA PFS, PFS and OS were reasonably long. Conclusions: PC pts with BRCA1/2 mutations had improved outcomes to PARPi compared to those with mutations in HRR genes not directly interacting with the BRCA complex. Platinum-based chemo appeared effective regardless of which HRR gene was affected.
Medical Subject Headings
Hematology
PubMed ID
Not assigned.
Volume
40
Issue
6 SUPPL
