Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/34573
Title: First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer: Clinical and Biomarker Results.
Austin Authors: Schmid, Peter;Turner, Nicholas C;Barrios, Carlos H;Isakoff, Steven Jay;Kim, Sung-Bae;Sablin, Marie-Paule;Saji, Shigehira;Savas, Peter;Vidal, Gregory A;Oliveira, Mafalda;O'Shaughnessy, Joyce;Italiano, Antoine;Espinosa, Enrique;Boni, Valentina;White, Shane ;Rojas, Beatriz;Freitas-Junior, Ruffo;Chae, Yeesoo;Bondarenko, Igor;Lee, Jieun;Torres Mattos, Cesar;Martinez Rodriguez, Jorge Luis;Lam, Lisa;Jones, Surai;Reilly, Sarah-Jayne;Huang, Xiayu;Shah, Kalpit;Dent, Rebecca
Affiliation: Barts Cancer Institute, London, United Kingdom.
Royal Marsden NHS Foundation Trust, London, United Kingdom.
Centro de Pesquisa em Oncologia, Hospital São Lucas, PUCRS Latin American Cooperative Oncology Group (LACOG), Porto Alegre, RS, Brazil.
Massachusetts General Hospital, Boston, MA, United States.
Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (South), Republic of.
Institute Curie, Paris, France.
Fukushima Medical University, Fukushima, Fukushima, Japan.
Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
West Cancer Center and Research Institute and University of Tennessee Health Science Center, Germantown, Tennessee, United States.
Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Barcelona, Spain.
Baylor University Medical Center, Texas Oncology, US Oncology, United States.
Institut Bergonié, Bordeaux, France.
Hospital Universitario La Paz- CIBERONC, Madrid, Madrid, Spain.
NEXT Madrid, Madrid, Spain.
Austin Health
Hospital Universitario HM Sanchinarro, Madrid, Spain.
Federal University of Goias, Goiania, Goias, Brazil.
Kyungpook National University Chilgok Hospital, Daegu, Korea (South), Republic of.
Dnipro State Medical University, Dnipro, Ukraine.
Seoul St. Mary's Hospital, Korea (South), Republic of.
Clínica San Marcos, Centro Especializado en Oncología de Precisión, Lima, Lima, Peru.
Christus Muguerza Clinica Vidriera, Mexico.
Genentech, Inc, South San Francisco, CA, United States.
IQVIA, South San Francisco, CA, United States.
Roche Products Ltd, Welwyn Garden City, United Kingdom.
gRED Computational Science, Roche (China) Holding Ltd, Shanghai, China.
Genentech, Inc., United States.
National Cancer Centre, Singapore, Singapore.
Issue Date: 7-Dec-2023
Date: 2023
Publication information: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research 2023-12-07
Abstract: 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). 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) 5.4-7.4 months, objective response rate 44-63%, median duration of response 5.6-11.1 months, and median overall survival 15.7-28.3 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. 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.
URI: https://ahro.austin.org.au/austinjspui/handle/1/34573
DOI: 10.1158/1078-0432.CCR-23-2084
ORCID: 0000-0001-9817-5228
0000-0001-8937-0873
0000-0001-6021-667X
0000-0002-6677-1014
0000-0001-5588-8332
0000-0003-4345-1576
0000-0002-6732-8030
0000-0001-5999-428X
0000-0003-3325-6224
0000-0001-9152-8799
0000-0002-2955-5523
0000-0002-8540-5351
0000-0001-6562-7902
0000-0002-8675-0018
0009-0003-6030-2801
0009-0005-6708-0214
0000-0003-4145-8598
0000-0002-8585-4982
0000-0002-7071-2471
0000-0002-2656-0650
0000-0003-4030-0457
0009-0008-8686-469X
0000-0001-5188-9522
0009-0001-5168-8904
0009-0001-9912-7428
0009-0004-7670-8336
0000-0001-6383-4625
0000-0001-6421-7602
Journal: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
PubMed URL: 38060199
ISSN: 1557-3265
Type: Journal Article
Appears in Collections:Journal articles

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