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

March 2019, Vol 9, No 3

Triple-negative breast cancer (TNBC) is considered one of the most difficult breast cancers to treat, with few therapeutic options. In an overall analysis of the phase 3 IMpassion130 trial, investigators showed that using the checkpoint inhibitor atezolizumab (Tecentriq), a PD-L1 inhibitor, with nab-paclitaxel (Abraxane) chemotherapy improved disease-free survival (DFS) and overall survival (OS) in patients with advanced or metastatic TNBC compared with placebo plus nab-paclitaxel. The survival benefit was even more robust in the PD-L1–positive cohort. These encouraging results were presented at the ESMO 2018 Congress and published in the New England Journal of Medicine.1

No Benefit In PD-L1–Negative Metastatic TNBC

More recently, a new exploratory analysis of the IMpassion130 trial has revealed that PD-L1–negative patients had no DFS or OS benefit from the immunotherapy-chemotherapy combination. This is a major finding, because checkpoint inhibitors appear to have an effect on other cancer types in PD-L1–positive as well as PD-L1–negative patients.

These new data, which were presented at the 2018 San Antonio Breast Cancer Symposium, support the use of atezolizumab/nab-paclitaxel exclusively in PD-L1–positive TNBC and strongly suggests 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/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,” she noted.

Matthew P. Goetz, MD, Co-leader, Women’s Cancer Program, Mayo Clinic Cancer Center, Rochester, MN, who was not involved in the study, said, “This analysis shows there is clearly zero benefit of atezolizumab/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 the Exploratory Analysis

Among PD-L1–negative patients, median progression-free survival was 5.6 months in both treatment arms (hazard ratio [HR], 0.94; P = .5152). By contrast, in PD-L1–positive patients, DFS was significantly improved with the use of immunotherapy versus placebo.

Median OS was comparable in both arms of PD-L1–negative patients: 18.9 months for those treated with atezolizumab/nab-paclitaxel and 18.4 months for those treated with placebo/nab-paclitaxel (HR, 1.02; P = .9068). However, in PD-L1–positive patients, median OS was 25.0 months for those assigned to atezolizumab/nab-paclitaxel compared with 15.5 months for those assigned to placebo/nab-paclitaxel (HR, 0.62; P = .0035).

The exploratory analysis also 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-L1­negative 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 atezolizumab/nab-paclitaxel therapy was PD-L1 expression of ≥1% in immune cells. Patients whose tumors expressed CD8+ T-cells and stromal TILs, as well as BRCA-positive patients, benefited from this 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/nab-paclitaxel,” Dr Emens said. “The take-away message is that higher levels of PD-L1 are not better. All levels of PD-L1 expression benefitted. PD-L1 expression on tumor cells did not provide additional information beyond PD-L1 expression on immune cells.”


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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