Atezolizumab/Nab-Paclitaxel of No Benefit in PD-L1–Negative Triple-Negative Breast Cancer

May 2019 Vol 10, No 5

Categories:

Breast Cancer

Atezolizumab plus nab-paclitaxel was the first immunotherapy combination to improve disease-free survival (DFS) and overall survival (OS) in women with metastatic triple-negative breast cancer (TNBC) versus placebo plus nab-paclitaxel in the overall analysis of the IMpassion130 trial. Survival improvement was even more robust in the PD-L1–positive cohort.

Results were greeted with enthusiasm when reported at ESMO 2018 and published in the New England Journal of Medicine.1

New Data

An exploratory analysis of the IMpassion130 study provides another important piece of news—PD-L1–negative patients enrolled in the trial had no DFS or OS benefit from the immunotherapy combination. This is a major finding, because checkpoint inhibitors appear to have an effect on other cancer types in PD-L1–positive and PD-L1–negative patients.

These findings, presented at the 2018 San Antonio Breast Cancer Symposium, support the use of atezolizu­mab plus nab-paclitaxel exclusively in patients with PD-L1–positive TNBC and strongly suggest that all patients with metastatic TNBC be tested for PD-L1 expression before treatment selection, according to experts interviewed for this article.

“Further analysis of results of IMpassion130 demonstrates that PD-L1 expression in immune cells is a highly reliable predictor of response. However, in PD-L1–negative patients, there is no treatment effect of atezolizumab plus nab-paclitaxel,” stated lead investigator Leisha A. Emens, MD, PhD, Director, Translational Immunotherapy, Women’s Cancer Research Center, UPMC Hillman Cancer Center, Pittsburgh, PA.

“This is brand new data. There is no treatment effect in PD-L1–negative patients, and the survival curves are superimposable.”

Zero Benefit for PD-L1–Negative Metastatic TNBC

Matthew P. Goetz, MD, Chair, Breast Cancer Disease-Oriented Group, Mayo Clinic Cancer Center, Rochester, MN, who was not involved in this study, said, “This analysis shows there is clearly zero benefit of atezolizumab plus nab-paclitaxel in PD-L1–negative patients. In PD-L1–positive patients, the combination improves progression-free survival and overall survival.”

“In other tumor types, we can’t exclude a benefit of checkpoint inhibitor in PD-L1–negative tumors. PD-L1–positive expression is a firm biomarker for patient selection for atezolizumab/nab-paclitaxel in this population,” he continued. “This analysis firmly cements the need for PD-L1 testing in TNBC.”

Details of Exploratory Analysis

Median progression-free survival was identical for both arms of the study in PD-L1–negative patients (5.6 months). By contrast, DFS was significantly improved by immunotherapy in the PD-L1–positive patients versus placebo.

Median OS was no different for either study arm in PD-L1–negative patients: 18.9 months for the immunotherapy combination and 18.4 months for placebo/nab-paclitaxel. By contrast, in PD-L1–positive patients, a 10-month advantage was observed for immunotherapy versus the placebo/nab-paclitaxel arm: median of 25.5 months versus 15.5 months, respectively.

The exploratory analysis evaluated the effect of immune biology (ie, CD8+ T cells, stromal tumor-infiltrating lymphocytes [TILs]) or BRCA on benefit from the checkpoint inhibitor combination in PD-L1–negative and –positive patients.

The majority of patients who were PD-L1–positive had PD-L1 expression on immune cells; only 2% had PD-L1 expression on tumor cells.

The threshold for benefit from the immunotherapy combination was PD-L1 expression of 1% or more in immune cells. Patients whose tumors expressed CD8+ T cells and stromal TILs, as well as BRCA-positive patients, benefited from the immunotherapy combination only if they were also PD-L1–positive.

“As long as the immune cells express PD-L1 of 1% or more, patients will benefit from atezolizumab plus nab-paclitaxel,” she said. “The takeaway message is that higher levels of PD-L1 are not better. All levels of PD-L1 expression benefited. PD-L1 expression on tumor cells did not provide additional information beyond PD-L1 expression on immune cells.”

IMpassion130 was sponsored by F. Hoffmann-La Roche, Ltd.

Reference

  1. Schmid P, Adams S, Rugo HS, et al; for the IMpassion130 trial investigators. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379:2108-2121.
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