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.
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Embargo End Date
ICR Authors
Authors
Dent, RA
Kim, S-B
Oliveira, M
Barrios, C
O'Shaughnessy, J
Isakoff, SJ
Saji, S
Freitas-Junior, R
Philco, M
Bondarenko, I
Lian, Q
Bradley, D
Hinton, H
Wongchenko, MJ
Reilly, S-J
Turner, N
Kim, S-B
Oliveira, M
Barrios, C
O'Shaughnessy, J
Isakoff, SJ
Saji, S
Freitas-Junior, R
Philco, M
Bondarenko, I
Lian, Q
Bradley, D
Hinton, H
Wongchenko, MJ
Reilly, S-J
Turner, N
Document Type
Journal Article
Date
2024-10-01
Date Accepted
2024-07-24
Abstract
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.
Citation
Clinical Cancer Research, 2024, 30 (19), pp. 4329 - 4338
Source Title
Clinical Cancer Research
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
1078-0432
eISSN
1557-3265
Collections
Research Team
Molecular Oncology