First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer: Clinical and Biomarker Results

Schmid, P; Turner, NC; Barrios, CH; Isakoff, SJ; Kim, SB; Sablin, MP; Saji, S; Savas, P; Vidal, GA; Oliveira, M; O&#39;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, SJ; Huang, X; Shah, K; Dent, R

Author(s): Schmid, P; Turner, NC; Barrios, CH; Isakoff, SJ; Kim, SB; Sablin, MP; 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, SJ; Huang, X; Shah, K; Dent, R;
Details: Publication Year 2024-02-16,Volume 30,Issue #4,Page 767-778
Journal Title: Clinical Cancer Research
Publication Type: Research article
Abstract: 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.
Publisher: American Association for Cancer Research
Keywords: Humans; *Triple Negative Breast Neoplasms/pathology; Proto-Oncogene Proteins c-akt; Taxoids/therapeutic use; Paclitaxel; Biomarkers, Tumor/metabolism; Antineoplastic Combined Chemotherapy Protocols/adverse effects; Albumins; *Bridged-Ring Compounds; *Piperazines; *Pyrimidines; *Antibodies, Monoclonal, Humanized
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1158/1078-0432.Ccr-23-2084
Open Access at Publisher's Site: https://doi.org/10.1158/1078-0432.Ccr-23-2084
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-03-26 02:54:47

Last Modified: 2024-03-26 02:55:34