DNA-Damaging Therapies in Patients With Prostate Cancer and Pathogenic Alterations in Homologous Recombination Repair Genes
Recommended Citation
Graham LS, Henderson NC, Kellezi O, Hwang C, Barata PC, Bilen MA, Kilari D, Pierro M, Thapa B, Tripathi A, Mo G, Labriola M, Park JJ, Rothstein S, Garje R, Koshkin VS, Patel VG, Dorff T, Armstrong AJ, McKay RR, Alva A, and Schweizer MT. DNA-Damaging Therapies in Patients With Prostate Cancer and Pathogenic Alterations in Homologous Recombination Repair Genes. JCO Precis Oncol 2024; 8:e2400014.
Document Type
Article
Publication Date
8-1-2024
Publication Title
JCO Precis Oncol
Abstract
PURPOSE: Outcomes data for DNA-damaging therapeutics for men with prostate cancer (PC) and non-BRCA1/2 homologous recombination repair (HRR) mutations are limited. We evaluated outcomes by HRR alteration in men with PC treated with poly(ADP-ribose)polymerase inhibitors (PARPi) and/or platinum chemotherapy.
METHODS: Retrospective data from the PROMISE consortium were used. Clinical outcomes differences were assessed between patients with BRCA1/2 mutations (cohort A) and those with HRR mutations without direct BRCA complex interaction (cohort B: ATM, CDK12, CHEK1, CHEK2, and FANCL). Outcomes in patients with HRR mutations with direct BRCA complex interaction were also explored (cohort C: RAD51B/C/D, RAD54L2, BARD1, GEN1, PALB2, FANCA, and BRIP1).
RESULTS: One hundred and forty-six patients received PARPi (cohort A: 94, cohort B: 45, cohort C: 7) and 104 received platinum chemotherapy (cohort A: 48, cohort B: 44, cohort C: 10). PSA50 response rate to PARPi was higher in cohort A (61%) than cohort B (5%), P < .001. Median clinical/radiographic progression-free survival (crPFS) with PARPi in cohort A was significantly longer than in cohort B: 15.9 versus 8.7 months, P = .005. PSA50 response rate to platinum therapy was higher in cohort A (62%) than in cohort B (32%), P = .024, although crPFS was not significantly different. PSA50 response rate to PARPi and platinum was 40% and 32%, respectively, in cohort C. In multivariable analysis, cohort A had significantly improved overall survival and crPFS compared with cohort B with PARPi but not platinum chemotherapy.
CONCLUSION: Patients with BRCA1/2-mutated PC had significantly improved outcomes to PARPi but not platinum chemotherapy compared with those with HRR mutations without direct BRCA complex interaction.
Medical Subject Headings
Humans; Male; Retrospective Studies; Aged; Middle Aged; Prostatic Neoplasms; Recombinational DNA Repair; Poly(ADP-ribose) Polymerase Inhibitors; Mutation; DNA Damage; Aged, 80 and over
PubMed ID
39178368
Volume
8
First Page
2400014
Last Page
2400014
