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Atezolizumab plus Nab-Paclitaxel for Triple-Negative Breast Cancer with PD-L1 Expression

TOP - May 2019, Vol 12, No 2
San Antonio, TX—Adding the PD-L1 inhibitor atezolizumab (Tecentriq) to nab-paclitaxel (Abraxane) chemother­apy is the first immunotherapy-based combination to improve progression-free survival (PFS) and overall survival (OS) in women with advanced or metastatic triple-negative breast cancer and PD-L1 expression compared with placebo plus nab-paclitaxel, according to results of the IMpassion130 clinical trial.

“Further analysis of the 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. She presented the study findings at the 2018 San Antonio Breast Cancer Symposium.

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

The IMpassion130 Study

An exploratory analysis of the IMpassion130 study provided important news that patients with PD-L1–negative disease who were enrolled in the trial had no survival benefit from the immunotherapy plus chemotherapy combination.

These findings support the use of atezolizumab plus nab-paclitaxel exclusively in patients with PD-L1–positive triple-negative breast cancer and strongly suggest that all patients with metastatic triple-negative breast cancer be tested for PD-L1 expression before treatment selection, according to experts who were interviewed for this article.

Role of PD-L1 Expression

“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,” said Matthew P. Goetz, MD, Chair, Breast Cancer Disease–Oriented Group, Mayo Clinic, Rochester, MN, who was not involved in this study.

“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 plus nab-paclitaxel in this population,” Dr Goetz continued. “This analysis firmly cements the need for PD-L1 testing in triple-negative breast cancer.”

The median PFS was identical (5.6 months) in both arms of the study in patients with PD-L1–negative disease. By contrast, PFS was significantly improved with the addition of immunotherapy in the PD-L1–positive patients versus placebo.

The median OS was similar in both study arms in patients without PD-L1 expression—18.9 months with the immunochemotherapy combination and 18.4 months with placebo plus nab-­paclitaxel. By contrast, in patients with PD-L1–positive disease, a 10-month OS advantage was seen in the immunotherapy arm versus the placebo plus nab-­paclitaxel arm (median, 25.5 months vs 15.5 months, respectively).

The exploratory analysis of IMpassion130 evaluated the effect of immune biology (ie, CD8+ T-cells, stromal tumor-infiltrating lymphocytes) or BRCA mutation on potential benefit from the checkpoint inhibitor plus chemotherapy combination in patients with PD-L1–negative or PD-L1–positive disease.

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

The threshold for benefit from the addition of immunotherapy was PD-L1 expression of ≥1% in immune cells. Patients whose tumors expressed CD8+ T-cells and stromal tumor-infiltrating lymphocytes, as well as patients with a BRCA mutation, benefited from the immunochemotherapy combination only if they also had PD-L1–positive disease.

“As long as the immune cells express PD-L1 of 1% or more, patients will benefit from atezolizumab plus nab-paclitaxel,” Dr Emens 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.”

Based on the results of the IMpassion130 clinical trial, on March 8, 2019, the FDA approved the combination of atezolizumab with nab-paclitaxel for the treatment of unresectable locally advanced or metastatic triple-negative breast cancer in patients with PD-L1 expression, as determined by the FDA-approved test, VENTANA PD-L1 (SP142) Assay, which was approved on the same day.

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