IMpassion130: PD-L1 Immune Cells Predictive of Survival Outcomes in Advanced TNBC

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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.
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.
The following article features coverage from the San Antonio Breast Cancer Symposium (SABCS) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.

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.”

Read more of Cancer Therapy Advisor's coverage of the SABCS 2018 meeting by visiting the conference page.

Reference

  1. 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.

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