dc.contributor.author | Ring, A | |
dc.contributor.author | Kilburn, LS | |
dc.contributor.author | Pearson, A | |
dc.contributor.author | Moretti, L | |
dc.contributor.author | Afshari-Mehr, A | |
dc.contributor.author | Wardley, AM | |
dc.contributor.author | Gurel, B | |
dc.contributor.author | Macpherson, IR | |
dc.contributor.author | Riisnaes, R | |
dc.contributor.author | Baird, RD | |
dc.contributor.author | Martin, S | |
dc.contributor.author | Roylance, R | |
dc.contributor.author | Johnson, H | |
dc.contributor.author | Ferreira, A | |
dc.contributor.author | Winter, MC | |
dc.contributor.author | Dunne, K | |
dc.contributor.author | Copson, E | |
dc.contributor.author | Hickish, T | |
dc.contributor.author | Burcombe, R | |
dc.contributor.author | Randle, K | |
dc.contributor.author | Serra, V | |
dc.contributor.author | Llop-Guevara, A | |
dc.contributor.author | Bliss, JM | |
dc.contributor.author | Turner, NC | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-10-11T10:19:07Z | |
dc.date.available | 2023-10-11T10:19:07Z | |
dc.date.issued | 2023-12-01 | |
dc.identifier | 729386 | |
dc.identifier.citation | Clinical Cancer Research, 2023, | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6011 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.CCR-23-1696 | |
dc.description.abstract | PURPOSE: Approximately 10% to 15% of triple-negative breast cancers (TNBC) have deleterious mutations in BRCA1 and BRCA2 and may benefit from PARP inhibitor treatment. PARP inhibitors may also increase exogenous replication stress and thereby increase sensitivity to inhibitors of ataxia telangiectasia and Rad3-related (ATR) protein. This phase II study examined the activity of the combination of PARP inhibitor, olaparib, and ATR inhibitor, ceralasertib (AZD6738), in patients with advanced TNBC. PATIENTS AND METHODS: Patients with TNBC on most recent biopsy who had received 1 or 2 lines of chemotherapy for advanced disease or had relapsed within 12 months of (neo)adjuvant chemotherapy were eligible. Treatment was olaparib 300 mg twice a day continuously and celarasertib 160 mg on days 1-7 on a 28-day cycle until disease progression. The primary endpoint was confirmed objective response rate (ORR). Tissue and plasma biomarker analyses were preplanned to identify predictors of response. RESULTS: 70 evaluable patients were enrolled. Germline BRCA1/2 mutations were present in 10 (14%) patients and 3 (4%) patients had somatic BRCA mutations. The confirmed ORR was 12/70; 17.1% (95% confidence interval, 10.4-25.5). Responses were observed in patients without germline or somatic BRCA1/2 mutations, including patients with mutations in other homologous recombination repair genes and tumors with functional homologous recombination deficiency by RAD51 foci. CONCLUSIONS: The response rate to olaparib and ceralasertib did not meet prespecified criteria for activity in the overall evaluable population, but responses were observed in patients who would not be expected to respond to olaparib monotherapy. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.relation.ispartof | Clinical Cancer Research | |
dc.title | Olaparib and Ceralasertib (AZD6738) in Patients with Triple-Negative Advanced Breast Cancer: Results from Cohort E of the plasmaMATCH Trial (CRUK/15/010). | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-09-26 | |
dc.date.updated | 2023-10-11T09:52:56Z | |
rioxxterms.version | AM | |
rioxxterms.versionofrecord | 10.1158/1078-0432.CCR-23-1696 | |
rioxxterms.licenseref.uri | http://creativecommons.org/licenses/by/4.0/ | |
rioxxterms.licenseref.startdate | 2023-09-29 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37773077 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.organisational-group | ICR/Students | |
pubs.organisational-group | ICR/Students/PhD and MPhil | |
pubs.organisational-group | ICR/Students/PhD and MPhil/18/19 Starting Cohort | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1158/1078-0432.ccr-23-1696 | |
icr.researchteam | Clin Trials & Stats Unit | |
icr.researchteam | Molecular Oncology | |
icr.researchteam | Cancer Biomarkers | |
dc.contributor.icrauthor | Kilburn, Lucy | |
dc.contributor.icrauthor | Pearson, Alex | |
dc.contributor.icrauthor | Gurel, Bora | |
dc.contributor.icrauthor | Bliss, Judith | |
dc.contributor.icrauthor | Turner, Nicholas | |
icr.provenance | Deposited by Mrs Jessica Perry (impersonating Prof Judith Bliss) on 2023-10-11. Deposit type is initial. No. of files: 2. Files: Supplementary for CCR_12_08_2023_amended_clean.pdf; Cohort E for CCR_12-08-2023_amended manusccript-clean.pdf | |