Leisha A. Emens, MD, PhD
Improvements observed in progression-free survival (PFS) and overall survival (OS) with the addition of first-line atezolizumab (Tecentriq) to nab-paclitaxel (Abraxane) in patients with metastatic triple negative breast cancer (TNBC) or inoperable locally advanced TNBC are exclusive to those patients with PD-L1 expression ≥1% in immune cells, according to a biomarker subgroup analysis of the phase III IMpassion130 study.1
Exploratory analyses of other biomarkers that included PD-L1 expression on tumor cells, intratumoral CD8+ T cells, stromal tumor-infiltrating lymphocytes, and BRCA1/2
mutation status, confirmed the importance of PD-L1 expression on immune cells in predicting clinical benefit derived from atezolizumab and nab-paclitaxel, said study co-author Leisha A. Emens, MD, PhD. She presented the data at the 2018 San Antonio Breast Cancer Symposium.
“PD-L1 expression on tumor cells did not provide additional information beyond PD-L1 immune cell status,” said Emens, professor of medicine in hematology/oncology and co-leader of the Hillman Cancer Immunology and Immunotherapy Program at the University of Pittsburgh Medical Center. “PD-L1 immune cell expression was the best predictor of clinical benefit as the patient subgroups with tumor-infiltrating immune cells or cytotoxic T cells derived clinical benefit with atezolizumab plus nab-paclitaxel if their tumors were also PD-L1 immune cell-positive. PFS and OS results were consistent regardless of BRCA1/2
The data support the routine testing for PD-L1 immune cell status to determine whether patients might benefit from atezolizumab plus nab-paclitaxel, she added.
PD-L1 in the IMpassion130 patient population was expressed primarily on tumor-infiltrating immune cells (41%). Twenty-seven percent had low levels at 1% to <5%, and 14% had levels in their immune cells at ≥5%. In contrast, only 9% of study had PD-L1 expression on tumor cells. Most of the patients with PD-L1 expression on tumor cells also had PD-L1 expression on their immune cells, Emens noted, with only 2% having PD-L1 expression exclusively on tumor cells.
Among the subgroup with PD-L1–negative immune cells, as first reported here, the median PFS was 5.6 months in both treatment arms (HR, 0.94; 95% CI, 0.78-1.13; P
The interaction between PD-L1 immune cell status and the difference in PFS between treatment arms was significant (P
A similar association was detected between PD-L1 status and OS in the subgroup with PD-L1-positive immune cells. The median OS was 25.0 months in the arm assigned to atezolizumab and nab-paclitaxel compared with 15.5 months in those assigned to placebo and nab-paclitaxel (HR, 0.62; 95% CI, 0.45-0.86; P
= .0035). There was no treatment effect observed in the PD-L1 immune cell-negative subpopulation, with a median OS of 18.9 months and 18.4 months, respectively (HR, 1.02; 95% CI, 0.79-1.31; P
The test for interaction between PD-L1 immune cell status and difference in OS between the treatment arm was significant (P
There were trends toward associations between PD-L1 immune cell positivity and worse PFS and OS.
“Taken together, these data definitively show that PD-L1 immune cell positivity is predictive of both PFS and OS benefit with atezolizumab and nab-paclitaxel,” Emens said.
The benefit to the combination on PFS and OS was significant in patients with low and high levels of PD-L1 expression on their immune cells. This suggests that an expression level of 1% may represent a threshold for identifying those benefits who are likely to benefit clinically from this combination,” Emens said.
IMpassion130 evaluated atezolizumab plus chemotherapy versus placebo and nab-paclitaxel in treatment-naïve patients with metastatic TNBC. Patients were randomized 1:1 to receive nab-paclitaxel at 100 mg/m2
intravenously on days 1, 8, and 15 of the 28-day cycle with atezolizumab at 840 mg intravenously (n = 451) on days 1 and 15 of a 28-day cycle or with placebo (n = 451). Treatment was given until disease progression or unacceptable toxicity.
The coprimary endpoints were PFS and OS in both the ITT and PD-L1–positive populations. PD-L1 expression was defined as positive if expression was at least 1% on tumor-infiltrating immune cells.
Other biomarker analyses performed in IMPassion130 were outcomes according to intratumoral CD8+ T cells by immunohistochemistry and stromal tumor-infiltrating lymphocytes by H&E, and BRCA1/2
“Pre-existing immune biology has been associated with clinical benefit from other agents that target the PD-1 pathway in other cancer types,” Emens said. “So, in these exploratory analyses, we sought to evaluate whether this immune biology as well as the BRCA1/2
mutation status were associated with clinical benefit from atezolizumab with nab-paclitaxel.”