dc.contributor.author | Schmid, P | |
dc.contributor.author | Turner, NC | |
dc.contributor.author | Barrios, CH | |
dc.contributor.author | Isakoff, SJ | |
dc.contributor.author | Kim, S-B | |
dc.contributor.author | Sablin, M-P | |
dc.contributor.author | Saji, S | |
dc.contributor.author | Savas, P | |
dc.contributor.author | Vidal, GA | |
dc.contributor.author | Oliveira, M | |
dc.contributor.author | O'Shaughnessy, J | |
dc.contributor.author | Italiano, A | |
dc.contributor.author | Espinosa, E | |
dc.contributor.author | Boni, V | |
dc.contributor.author | White, S | |
dc.contributor.author | Rojas, B | |
dc.contributor.author | Freitas-Junior, R | |
dc.contributor.author | Chae, Y | |
dc.contributor.author | Bondarenko, I | |
dc.contributor.author | Lee, J | |
dc.contributor.author | Torres Mattos, C | |
dc.contributor.author | Martinez Rodriguez, JL | |
dc.contributor.author | Lam, LH | |
dc.contributor.author | Jones, S | |
dc.contributor.author | Reilly, S-J | |
dc.contributor.author | Huang, X | |
dc.contributor.author | Shah, K | |
dc.contributor.author | Dent, R | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2024-03-01T11:28:49Z | |
dc.date.available | 2024-03-01T11:28:49Z | |
dc.date.issued | 2024-02-16 | |
dc.identifier | 731585 | |
dc.identifier.citation | Clinical Cancer Research, 2024, 30 (4), pp. 767 - 778 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6171 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.CCR-23-2084 | |
dc.identifier.doi | 10.1158/1078-0432.CCR-23-2084 | |
dc.description.abstract | PURPOSE: To evaluate a triplet regimen combining immune checkpoint blockade, AKT pathway inhibition, and (nab-) paclitaxel as first-line therapy for locally advanced/metastatic triple-negative breast cancer (mTNBC). PATIENTS AND METHODS: The single-arm CO40151 phase Ib study (NCT03800836), the single-arm signal-seeking cohort of IPATunity130 (NCT03337724), and the randomized phase III IPATunity170 trial (NCT04177108) enrolled patients with previously untreated mTNBC. Triplet therapy comprised intravenous atezolizumab 840 mg (days 1 and 15), oral ipatasertib 400 mg/day (days 1-21), and intravenous paclitaxel 80 mg/m2 (or nab-paclitaxel 100 mg/m2; days 1, 8, and 15) every 28 days. Exploratory translational research aimed to elucidate mechanisms and molecular markers of sensitivity and resistance. RESULTS: Among 317 patients treated with the triplet, efficacy ranged across studies as follows: median progression-free survival (PFS) 5.4 to 7.4 months, objective response rate 44% to 63%, median duration of response 5.6 to 11.1 months, and median overall survival 15.7 to 28.3 months. The safety profile was consistent with the known toxicities of each agent. Grade ≥3 adverse events were more frequent with the triplet than with doublets or single-agent paclitaxel. Patients with PFS >10 months were characterized by NF1, CCND3, and PIK3CA alterations and increased immune pathway activity. PFS <5 months was associated with CDKN2A/CDKN2B/MTAP alterations and lower predicted phosphorylated AKT-S473 levels. CONCLUSIONS: In patients with mTNBC receiving an ipatasertib/atezolizumab/taxane triplet regimen, molecular characteristics may identify those with particularly favorable or unfavorable outcomes, potentially guiding future research efforts. | |
dc.format | Print | |
dc.format.extent | 767 - 778 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.relation.ispartof | Clinical Cancer Research | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.title | First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer: Clinical and Biomarker Results. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-12-05 | |
dc.date.updated | 2024-03-01T11:28:27Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1158/1078-0432.CCR-23-2084 | |
rioxxterms.licenseref.startdate | 2024-02-16 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/38060199 | |
pubs.issue | 4 | |
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.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1158/1078-0432.ccr-23-2084 | |
pubs.volume | 30 | |
icr.researchteam | Molecular Oncology | |
dc.contributor.icrauthor | Turner, Nicholas | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Andrew McKean) on 2024-03-01. Deposit type is initial. No. of files: 1. Files: 767.pdf | |