Dataset Information

Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial-Efficacy and Biomarker Discovery.

ABSTRACT:

Purpose

The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial.

Patients and methods

I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2). The primary endpoint is pathologic complete response (pCR). A therapy "graduates" if/when it achieves 85% Bayesian probability of success in a phase III trial within a given subtype. Patients received weekly paclitaxel (plus trastuzumab if HER2-positive) without (control) or with weekly intravenous trebananib, followed by doxorubicin/cyclophosphamide and surgery. Pathway-specific biomarkers were assessed for response prediction.

Results

There were 134 participants randomized to trebananib and 133 to control. Although trebananib did not graduate in any signature [phase III probabilities: Hazard ratio (HR)-negative (78%), HR-negative/HER2-positive (74%), HR-negative/HER2-negative (77%), and MP2 (79%)], it demonstrated high probability of superior pCR rates over control (92%-99%) among these subtypes. Trebananib improved 3-year event-free survival (HR 0.67), with no significant increase in adverse events. Activation levels of the Tie2 receptor and downstream signaling partners predicted trebananib response in HER2-positive disease; high expression of a CD8 T-cell gene signature predicted response in HR-negative/HER2-negative disease.

Conclusions

The angiopoietin (Ang)/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority >90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted.

SUBMITTER: Albain KS

PROVIDER: S-EPMC10956403 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial-Efficacy and Biomarker Discovery.

Albain Kathy S KS Yau Christina C Petricoin Emanuel F EF Wolf Denise M DM Lang Julie E JE Chien A Jo AJ Haddad Tufia T Forero-Torres Andres A Wallace Anne M AM Kaplan Henry H Pusztai Lajos L Euhus David D Nanda Rita R Elias Anthony D AD Clark Amy S AS Godellas Constantine C Boughey Judy C JC Isaacs Claudine C Tripathy Debu D Lu Janice J Yung Rachel L RL Gallagher Rosa I RI Wulfkuhle Julia D JD Brown-Swigart Lamorna L Krings Gregor G Chen Yunn Yi YY Potter David A DA Stringer-Reasor Erica E Blair Sarah S Asare Smita M SM Wilson Amy A Hirst Gillian L GL Singhrao Ruby R Buxton Meredith M Clennell Julia L JL Sanil Ashish A Berry Scott S Asare Adam L AL Matthews Jeffrey B JB DeMichele Angela M AM Hylton Nola M NM Melisko Michelle M Perlmutter Jane J Rugo Hope S HS Symmans W Fraser WF Van't Veer Laura J LJ Yee Douglas D Berry Donald A DA Esserman Laura J LJ

Clinical cancer research : an official journal of the American Association for Cancer Research 20240201 4

<h4>Purpose</h4>The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial.<h4>Patients and methods</h4>I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone ...[more]

PMID: 38109213

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Dataset Information

Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial-Efficacy and Biomarker Discovery.

Purpose

Patients and methods

Results

Conclusions

Publications

Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial-Efficacy and Biomarker Discovery.

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