First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer: Clinical and Biomarker Results.
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Date
2024-02-16ICR Author
Author
Schmid, P
Turner, NC
Barrios, CH
Isakoff, SJ
Kim, S-B
Sablin, M-P
Saji, S
Savas, P
Vidal, GA
Oliveira, M
O'Shaughnessy, J
Italiano, A
Espinosa, E
Boni, V
White, S
Rojas, B
Freitas-Junior, R
Chae, Y
Bondarenko, I
Lee, J
Torres Mattos, C
Martinez Rodriguez, JL
Lam, LH
Jones, S
Reilly, S-J
Huang, X
Shah, K
Dent, R
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Research team
Molecular Oncology
Language
eng
Date accepted
2023-12-05
License start date
2024-02-16
Citation
Clinical Cancer Research, 2024, 30 (4), pp. 767 - 778
Publisher
AMER ASSOC CANCER RESEARCH