2026-04-14T02:49:12Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/122252025-10-24T02:03:10Zcom_2072_378070com_2072_378040col_2072_378092

urn:hdl:11351/12225 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 Kim, Sung-Bae Barrios, Carlos O'Shaughnessy, Joyce Isakoff, Steven Oliveira, Mafalda Dent, Rebecca 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: Triple-negative breast cancer Ipatasertib; Cáncer de mama triple negativo Ipatasertib; Càncer de mama triple negatiu Purpose: 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. 2024-11-14T13:42:41Z 2024-11-14T13:42:41Z 2024-10-01 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Clinical Cancer Research;30(19) https://doi.org/10.1158/1078-0432.CCR-24-0465 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess American Association for Cancer Research Scientia