dc.contributor.author | Turner, N | |
dc.contributor.author | Dent, RA | |
dc.contributor.author | O'Shaughnessy, J | |
dc.contributor.author | Kim, S-B | |
dc.contributor.author | Isakoff, SJ | |
dc.contributor.author | Barrios, C | |
dc.contributor.author | Saji, S | |
dc.contributor.author | Bondarenko, I | |
dc.contributor.author | Nowecki, Z | |
dc.contributor.author | Lian, Q | |
dc.contributor.author | Reilly, S-J | |
dc.contributor.author | Hinton, H | |
dc.contributor.author | Wongchenko, MJ | |
dc.contributor.author | Kovic, B | |
dc.contributor.author | Mani, A | |
dc.contributor.author | Oliveira, M | |
dc.coverage.spatial | Netherlands | |
dc.date.accessioned | 2021-12-15T14:33:56Z | |
dc.date.available | 2021-12-15T14:33:56Z | |
dc.date.issued | 2021-12-03 | |
dc.identifier | https://www.ncbi.nlm.nih.gov/pubmed/34860318 | |
dc.identifier | 10.1007/s10549-021-06450-x | |
dc.identifier.citation | Breast Cancer Res Treat, 2021 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4926 | |
dc.identifier.eissn | 1573-7217 | |
dc.identifier.doi | 10.1007/s10549-021-06450-x | |
dc.description.abstract | PURPOSE: PI3K/AKT pathway alterations are frequent in hormone receptor-positive (HR+) breast cancers. IPATunity130 Cohort B investigated ipatasertib-paclitaxel in PI3K pathway-mutant HR+ unresectable locally advanced/metastatic breast cancer (aBC). METHODS: Cohort B of the randomized, double-blind, placebo-controlled, phase 3 IPATunity130 trial enrolled patients with HR+ HER2-negative PIK3CA/AKT1/PTEN-altered measurable aBC who were considered inappropriate for endocrine-based therapy (demonstrated insensitivity to endocrine therapy or visceral crisis) and were candidates for taxane monotherapy. Patients with prior chemotherapy for aBC or relapse < 1 year since (neo)adjuvant chemotherapy were ineligible. Patients were randomized 2:1 to ipatasertib (400 mg, days 1-21) or placebo, plus paclitaxel (80 mg/m2, days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS). RESULTS: Overall, 146 patients were randomized to ipatasertib-paclitaxel and 76 to placebo-paclitaxel. In both arms, median investigator-assessed PFS was 9.3 months (hazard ratio, 1.00, 95% CI 0.71-1.40) and the objective response rate was 47%. Median paclitaxel duration was 6.9 versus 8.8 months in the ipatasertib-paclitaxel versus placebo-paclitaxel arms, respectively; median ipatasertib/placebo duration was 8.0 versus 9.1 months, respectively. The most common grade ≥ 3 adverse events were diarrhea (12% with ipatasertib-paclitaxel vs 1% with placebo-paclitaxel), neutrophil count decreased (9% vs 7%), neutropenia (8% vs 9%), peripheral neuropathy (7% vs 3%), peripheral sensory neuropathy (3% vs 5%) and hypertension (1% vs 5%). CONCLUSION: Adding ipatasertib to paclitaxel did not improve efficacy in PIK3CA/AKT1/PTEN-altered HR+ HER2-negative aBC. The ipatasertib-paclitaxel safety profile was consistent with each agent's known adverse effects. Trial registration NCT03337724. | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | SPRINGER | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | First-line | |
dc.subject | HER2 negative | |
dc.subject | Hormone receptor positive | |
dc.subject | Ipatasertib | |
dc.subject | PI3K/AKT | |
dc.title | Ipatasertib plus paclitaxel for PIK3CA/AKT1/PTEN-altered hormone receptor-positive HER2-negative advanced breast cancer: primary results from cohort B of the IPATunity130 randomized phase 3 trial. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-11-12 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1007/s10549-021-06450-x | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2021-12-03 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Breast Cancer Res Treat | |
pubs.notes | Not known | |
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 online | |
pubs.embargo.terms | Not known | |
icr.researchteam | Molecular Oncology | |
dc.contributor.icrauthor | Turner, Nicholas | |