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Association details:
| Biomarker: | CHEK2 mutation |
|---|---|
| Cancer: | Prostate Cancer |
| Drug: | Lynparza (olaparib) (PARP inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Excerpt:
Olaparib is a treatment option for patients with mCRPC and a pathogenic mutaion (germline /somatic) in a homologous recombination repair gene (BRCA1, BRCA2, ATM, BADR1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D or RAD54L) who have been treated with androgen-receptor therapy.
Source:
Title:
Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis
Excerpt:
...For enrichment stage of trial only (if necessary): Confirmation of a suspected/known deleterious mutation in a gene of interest (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, or other DNA repair genes) via CLIA certified testing....
Trial ID:
Source:
Title:
The Study of Olaparib Combined With Abiraterone and Prednisone in mHSPC Patients With HRR Gene Mutation
Excerpt:
...- Qualifying HRR gene mutations (deleterious or suspected deleterious gene alterations) are BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD 51C, RAD51D and RAD54L mutations confirmed by the central lab....
Trial ID:
More C2 evidence
Source:
Title:
The Study of Olaparib in Newly Diagnosed mCRPC Patients With HRR Gene Mutation
Excerpt:
...- Qualifying HRR gene mutations (deleterious or suspected deleterious gene alterations) are BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD 51C, RAD51D and RAD54L mutations confirmed by the central lab....
Trial ID:
Source:
Title:
Olaparib Maintenance in Patients With MCRPC After Docetaxel Treatment Reaching Partial or Stable Response (IMANOL)
Excerpt:
...- Documented germline/somatic mutation in any of the Homologous Recombination Repair genes, including among others, BRCA1 or BRCA2, ATM, Fanconi genes, CHEK2, mutL homolog 1 (MLH1), mutS homologue 2 (MSH2), mutS homolog 6 (MSH6), PMS2, PALB2, RAD51C, MRE11 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)....
Trial ID:
Less C2 evidence
Source:
Title:
TOPARP-B: A phase II randomized trial of the poly(ADP)-ribose polymerase (PARP) inhibitor olaparib for metastatic castration resistant prostate cancers (mCRPC) with DNA damage repair (DDR) alterations.
Excerpt:
The overall RR was 54%...the overall median PFS (mPFS) was 5.4 mo. Subgroup analyses per altered gene identified indicated response rates for: others [ATRX, CHEK1, CHEK2, FANCA, FANCF, FANCG, FANCI, FANCM, RAD50, WRN] 20% (4/20; mPFS 2.8mo)… Olaparib has antitumor activity against heavily pre-treated mCRPC with DDR gene defects, with BRCA1/2 aberrant tumors being most sensitive but with confirmed responses in patients with other DDR alterations.
DOI:
10.1200/JCO.2019.37.15_suppl.5005
Trial ID:
Source:
Title:
DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer
Excerpt:
Sixteen of 49 patients who could be evaluated had a response (33%; 95% confidence interval, 20 to 48), with 12 patients receiving the study treatment for more than 6 months. Next-generation sequencing identified homozygous deletions, deleterious mutations, or both in DNA-repair genes--including BRCA1/2, ATM, Fanconi's anemia genes, and CHEK2--in 16 of 49 patients who could be evaluated (33%). Of these 16 patients, 14 (88%) had a response to olaparib, including all 7 patients with BRCA2 loss (4 with biallelic somatic loss, and 3 with germline mutations) and 4 of 5 with ATM aberrations.
DOI:
10.1056/NEJMoa1506859
Trial ID:
