2026-04-13T05:05:27Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/122252025-10-24T02:03:10Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
Kim, Sung-Bae
author
Barrios, Carlos
author
O'Shaughnessy, Joyce
author
Isakoff, Steven
author
Oliveira, Mafalda
author
Dent, Rebecca
2024-11-14T13:42:41Z2024-11-14T13:42:41Z2024-10-01
Ipatasertib: Triple-negative breast cancerIpatasertib; Cáncer de mama triple negativoIpatasertib; Càncer de mama triple negatiuPurpose:
In the randomized phase II LOTUS trial, combining ipatasertib with first-line paclitaxel for triple-negative breast cancer (TNBC) improved progression-free survival (PFS), particularly in patients with PIK3CA/AKT1/PTEN-altered tumors. We aimed to validate these findings in a biomarker-selected TNBC population.
Patients and Methods:
In Cohort A of the randomized double-blind placebo-controlled phase III IPATunity130 trial, taxane-eligible patients with PIK3CA/AKT1/PTEN-altered measurable advanced TNBC and no prior chemotherapy for advanced disease were randomized 2:1 to ipatasertib (400 mg, days 1–21) or placebo, both plus paclitaxel (80 mg/m2, days 1, 8, and 15), every 28 days until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed PFS.
Results:
Between February 2018 and April 2020, 255 patients were randomized (168 to ipatasertib, 87 to placebo). At the primary analysis, there was no significant difference between treatment arms in PFS [hazard ratio 1.02, 95% confidence interval (CI), 0.71–1.45; median 7.4 months with ipatasertib vs. 6.1 months with placebo]. The final analysis showed no difference in overall survival between treatment arms (hazard ratio 1.08, 95% CI, 0.73–1.58; median 24.4 vs. 24.9 months, respectively). Ipatasertib was associated with more grade ≥3 diarrhea (9% vs. 2%) and adverse events leading to dose reduction (39% vs. 14%) but similar incidences of grade ≥3 adverse events (51% vs. 46%). Exploratory subgroup analyses by PAM50 and Burstein gene expression showed inconsistent results.
Conclusions:
Adding ipatasertib to paclitaxel did not improve efficacy in PIK3CA/AKT1/PTEN-altered advanced TNBC. Biomarkers for benefit from PI3K/AKT pathway inhibition in TNBC remain poorly understood.This work was supported by Genentech/Roche. Medical writing assistance was provided by Jennifer Kelly, MA (Medi-Kelsey Ltd.), funded by F. Hoffmann-La Roche Ltd., Basel, Switzerland. No grant number is applicable.
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess
Mama - Càncer - Tractament
Quimioteràpia combinada
Marcadors tumorals
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales
Ipatasertib plus Paclitaxel for Patients with PIK3CA/AKT1/PTEN-Altered Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer in the IPATunity130 Phase III Trial
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion