First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer : Clinical and Biomarker Results
©2023 The Authors; Published by the American Association for Cancer Research..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Clinical cancer research : an official journal of the American Association for Cancer Research - 30(2024), 4 vom: 16. Feb., Seite 767-778 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schmid, Peter [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.02.2024 Date Revised 14.03.2024 published: Print ClinicalTrials.gov: NCT03800836 Citation Status MEDLINE |
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| doi: |
10.1158/1078-0432.CCR-23-2084 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365510971 |
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| 245 | 1 | 0 | |a First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer |b Clinical and Biomarker Results |
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| 500 | |a Date Revised 14.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT03800836 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a ©2023 The Authors; Published by the American Association for Cancer Research. | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
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