Related Experiment Video
Updated: Nov 19, 2025
Patient-Derived Tumor Explants As a "Live" Preclinical Platform for Predicting Drug Resistance in Patients
Published on: February 7, 2021
Atezolizumab and nab-Paclitaxel in Advanced Triple-Negative Breast Cancer: Biomarker Evaluation of the IMpassion130
Leisha A Emens1, Luciana Molinero2, Sherene Loi3
1University of Pittsburgh Medical Center, Hillman Cancer Center/Magee Women's Hospital, Pittsburgh, PA, USA.
Background:
Understanding the impact of the tumor immune microenvironment and BRCA1/2-related DNA repair deficiencies on the clinical activity of immune checkpoint inhibitors may help optimize both patient and treatment selection in metastatic triple-negative breast cancer. In this substudy from the phase 3 IMpassion130 trial, immune biomarkers and BRCA1/2 alterations were evaluated for association with clinical benefit with atezolizumab and nab-paclitaxel (A+nP) vs placebo and nP in unresectable (P+nP) locally advanced or metastatic triple-negative breast cancer.
Methods:
Patients were randomly assigned 1:1 to nab-paclitaxel 100 mg/m2 (days 1, 8, and 15 of a 28-day cycle) and atezolizumab 840 mg every 2 weeks or placebo until progression or toxicity. Progression-free survival and overall survival were evaluated based on programmed death-ligand 1 (PD-L1) expression on immune cells (IC) and tumor cells, intratumoral CD8, stromal tumor-infiltrating lymphocytes, and BRCA1/2 mutations.
Results:
PD-L1 IC+ in either primary or metastatic tumor tissue was linked to progression-free survival and overall survival benefit with A+nP. PD-L1 IC+ low (26.9%; 243 of 902 patients) and high (13.9%; 125 of 902 patients) populations had improved outcomes that were comparable. Intratumoral CD8 and stromal tumor-infiltrating lymphocytes positivity (sTIL+) were associated with PD-L1 IC+ status; improved outcomes were observed with A+nP vs P+nP only in CD8+ and sTIL+ patients who were also PD-L1 IC+. BRCA1/2 mutations (occurring in 14.5% [89 of 612 patients]) were not associated with PD-L1 IC status, and PD-L1 IC+ patients benefited from A+nP regardless of BRCA1/2 mutation status.
Conclusions:
Although A+nP was more efficacious in patients with richer tumor immune microenvironment, clinical benefit was only observed in patients whose tumors were PD-L1 IC+.
Insights
Immune checkpoint inhibitors like atezolizumab plus nab-paclitaxel improved outcomes in metastatic triple-negative breast cancer patients with PD-L1 expression. BRCA1/2 mutations did not impact benefit, highlighting PD-L1 status as key for treatment selection.
Area of Science:
- Oncology
- Immunotherapy
- Genetics
Background:
- Metastatic triple-negative breast cancer (mTNBC) treatment is challenging.
- Understanding the tumor immune microenvironment (TME) and DNA repair deficiencies (e.g., BRCA1/2) is crucial for optimizing immune checkpoint inhibitor (ICI) therapy.
- The IMpassion130 trial investigated atezolizumab plus nab-paclitaxel (A+nP) in mTNBC.
Purpose of the Study:
- To evaluate the impact of TME biomarkers and BRCA1/2 alterations on clinical activity of A+nP versus placebo plus nab-paclitaxel (P+nP).
- To identify patient subgroups who benefit most from A+nP in mTNBC.
Main Methods:
- Substudy of the phase 3 IMpassion130 trial.
- Randomized patients to A+nP or P+nP.
- Assessed progression-free survival (PFS) and overall survival (OS) based on PD-L1 expression (immune cells [IC] and tumor cells), CD8+ T-cell infiltration, stromal tumor-infiltrating lymphocytes (sTILs), and BRCA1/2 mutations.
Main Results:
- PD-L1 expression on immune cells (IC+) correlated with PFS and OS benefit for A+nP.
- Improved outcomes with A+nP were observed in both PD-L1 IC+ low and high expressors.
- CD8+ and sTIL+ positivity were associated with PD-L1 IC+ status; benefit was seen only in PD-L1 IC+ patients.
- BRCA1/2 mutations (14.5%) were not associated with PD-L1 IC status, and PD-L1 IC+ patients benefited regardless of BRCA1/2 status.
Conclusions:
- A+nP demonstrated efficacy in mTNBC, particularly in patients with PD-L1 IC+ tumors.
- While a richer TME (CD8+, sTILs) correlated with PD-L1 IC+ status, PD-L1 expression was the primary determinant of clinical benefit.
- BRCA1/2 mutation status did not influence the benefit of A+nP in PD-L1 IC+ patients.
