IMpassion130: PD-L1 Immune Cells Predictive of Survival Outcomes in Advanced TNBC
PD-L1 expression by tumor-infiltrating immune cells was found to be the most predictive biomarker for survival outcomes for patients with advanced TNBC in the IMpassion130 trial.
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PD-L1 tumor expression predicted survival outcomes among patients with advanced triple-negative breast cancer (TNBC) treated with atezolizumab plus nab-paclitaxel in the IMpassion130 study, according to data presented at the 2018 San Antonio Breast Cancer Symposium in Texas.1
It was previously reported that the phase 3 IMpassion130 trial (ClinicalTrials.gov Identifier: NCT02425891) met its coprimary endpoints of progression-free survival (PFS) in the intention-to-treat and PD-L1 greater than or equal to 1% tumor-infiltrating immune cells (ICs) populations. The purpose of this study was to evaluate exploratory efficacy data and biomarker-defined subgroups.
During the IMpassion130 trial, 902 patients with metastatic or unresectable locally advanced TNBC were randomly assigned to receive first-line atezolizumab plus nab-paclitaxel or placebo plus nab-paclitaxel until unacceptable toxicity or disease progression. Exploratory biomarkers included PD-L1 tumor expression by the Ventana SP142 immunohistochemistry assay, intratumoral CD8, stromal tumor-infiltrating lymphocytes (sTILs), and status of BRCA1/2, hormone receptors, and HER2.
Among the 900 patients evaluable for these exploratory analyses, most tumors that expressed PD-L1 were also positive for PD-L1 ICs. Patients with PD-L1 expression experienced a significant improvement in both PFS and OS.
The median PFS in the atezolizumab group was 7.5 months (95% CI, 6.7-9.2 months) compared with 5.0 months (95% CI, 3.8-5.6 months) with placebo among patients with PD-L1-positive ICs (hazard ratio [HR], 0.62; 95% CI, 0.49-0.78; P < .0001). This benefit was also observed among patients with PD-L1 tumor expression (HR, 0.51; 95% CI, 0.38-0.84).
OS was improved in the atezolizumab group in the PD-L1-positive IC population, with a median of 25.0 months (95% CI, 22.6-not evaluable) compared with 15.5 months (95% CI, 13.1-19.4 months) in the placebo group (HR, 0.62; 95% CI, 0.45-0.86), though this endpoint was not formally tested per hierarchical study design. In the population with PD-L1 tumor expression, however, there was no OS difference between groups (HR, 0.63; 95% CI, 0.33-1.21).
Intratumoral CD8 correlated with PD-L1 IC expression, and was therefore predictive of prolonged PFS (HR, 0.74; 95% CI, 0.61-0.91) and OS (HR, 0.66; 95% CI, 0.50-0.88) outcomes with atezolizumab plus nab-paclitaxel versus placebo and nab-paclitaxel. sTILs were not well-correlated with PD-L1 IC expression, and only predicted prolonged PFS with atezolizumab compared with placebo (HR, 0.66; 95% CI, 0.50-0.86).
The authors concluded that these exploratory analyses suggest “that PD-L1 IC is the most robust predictive biomarker for selecting untreated metastatic TNBC patients who benefit from atezolizumab and nab-paclitaxel.”
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- Emens LA, Loi S, Rugo HS, et al. IMpassion130: Efficacy in immune biomarker subgroups from the global, randomized, double-blind, placebo-controlled, phase III study of atezolizumab + nab-paclitaxel in patients with treatment-naïve, locally advanced or metastatic triple-negative breast cancer. Presented at: 2018 San Antonio Breast Cancer Symposium; San Antonio, TX: December 4-8, 2018. Abstract GS1-04.