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DNA damaging therapies in patients (pts) with prostate cancer (PC) and pathogenic alterations in homologous recombination repair (HRR) genes.

Publication ,  Conference
Graham, L; Green, E; Park, JJ; Kellezi, O; Hwang, C; Barata, PC; Bilen, MA; Kilari, D; Clingerman, M; Tripathi, A; Labriola, M; Rothstein, S ...
Published in: Journal of Clinical Oncology
February 20, 2022

129 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. [Table: see text]

Duke Scholars

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 20, 2022

Volume

40

Issue

6_suppl

Start / End Page

129 / 129

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Graham, L., Green, E., Park, J. J., Kellezi, O., Hwang, C., Barata, P. C., … Schweizer, M. T. (2022). DNA damaging therapies in patients (pts) with prostate cancer (PC) and pathogenic alterations in homologous recombination repair (HRR) genes. In Journal of Clinical Oncology (Vol. 40, pp. 129–129). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2022.40.6_suppl.129
Graham, Laura, Edward Green, Joseph J. Park, Olesia Kellezi, Clara Hwang, Pedro C. Barata, Mehmet Asim Bilen, et al. “DNA damaging therapies in patients (pts) with prostate cancer (PC) and pathogenic alterations in homologous recombination repair (HRR) genes.” In Journal of Clinical Oncology, 40:129–129. American Society of Clinical Oncology (ASCO), 2022. https://doi.org/10.1200/jco.2022.40.6_suppl.129.
Graham L, Green E, Park JJ, Kellezi O, Hwang C, Barata PC, et al. DNA damaging therapies in patients (pts) with prostate cancer (PC) and pathogenic alterations in homologous recombination repair (HRR) genes. In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2022. p. 129–129.
Graham, Laura, et al. “DNA damaging therapies in patients (pts) with prostate cancer (PC) and pathogenic alterations in homologous recombination repair (HRR) genes.Journal of Clinical Oncology, vol. 40, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2022, pp. 129–129. Crossref, doi:10.1200/jco.2022.40.6_suppl.129.
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. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2022. p. 129–129.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 20, 2022

Volume

40

Issue

6_suppl

Start / End Page

129 / 129

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences