TY - JOUR
T1 - First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer
T2 - Clinical and Biomarker Results
AU - Schmid, Peter
AU - Turner, Nicholas C.
AU - Barrios, Carlos H.
AU - Isakoff, Steven J.
AU - Kim, Sung Bae
AU - Sablin, Marie Paule
AU - Saji, Shigehira
AU - Savas, Peter
AU - Vidal, Gregory A.
AU - Oliveira, Mafalda
AU - O'Shaughnessy, Joyce
AU - Italiano, Antoine
AU - Espinosa, Enrique
AU - Boni, Valentina
AU - White, Shane
AU - Rojas, Beatriz
AU - Freitas-Junior, Ruffo
AU - Chae, Yeesoo
AU - Bondarenko, Igor
AU - Lee, Jieun
AU - Mattos, Cesar Torres
AU - Rodriguez, Jorge Luis Martinez
AU - Lam, Lisa H.
AU - Jones, Surai
AU - Reilly, Sarah Jayne
AU - Huang, Xiayu
AU - Shah, Kalpit
AU - Dent, Rebecca
N1 - Publisher Copyright:
© 2023 The Authors.
PY - 2024/2/15
Y1 - 2024/2/15
N2 - Purpose: To evaluate a triplet regimen combining immune checkpoint blockade, AKT pathway inhibition, and (nab-) paclitaxel as first-line therapy for locally advanced/metastatic triplenegative 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 wasconsistent with theknown 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.
AB - Purpose: To evaluate a triplet regimen combining immune checkpoint blockade, AKT pathway inhibition, and (nab-) paclitaxel as first-line therapy for locally advanced/metastatic triplenegative 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 wasconsistent with theknown 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.
UR - http://www.scopus.com/inward/record.url?scp=85185215719&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-23-2084
DO - 10.1158/1078-0432.CCR-23-2084
M3 - Article
C2 - 38060199
AN - SCOPUS:85185215719
SN - 1078-0432
VL - 30
SP - 767
EP - 778
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 4
ER -