medwireNews: The addition of pembrolizumab to eribulin does not improve the survival outcomes of patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, suggests a phase 2 study.
Sara Tolaney (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and colleagues explain in JAMA Oncology that despite the “promising antitumor activity” of this combination in patients with metastatic triple-negative breast cancer, their results “do not support” its use in patients with HR-positive, HER2-negative metastatic breast cancer, regardless of PD-L1 status.
The study included 88 patients who had received up to two prior lines of chemotherapy for metastatic disease and at least two lines of endocrine therapy. Participants were randomly assigned to receive pembrolizumab 200 mg/m2 on day 1 of each 21-day cycle plus eribulin 1.4 mg/m2 on days 1 and 8 (n=44) or eribulin alone (n=44).
After a median follow-up of 10.5 months, there was no significant difference in median progression-free survival (PFS) between the two treatment groups, at 4.1 months for the combination-treated patients and 4.2 months for those who received eribulin monotherapy.
Median overall survival was similarly comparable between the combination and eribulin alone treatment groups, at 13.4 and 12.5 months, respectively, and so was the objective response rate (ORR), at a corresponding 27% and 34%.
Tolaney et al note, however, that “the ORR seen in the control arm of this study is higher than previously reported for eribulin in this setting.”
Fourteen of the study participants started pembrolizumab after progressing on eribulin monotherapy, but only one patient experienced stable disease lasting for 4.3 months.
Exploratory analysis showed no association between improved PFS and PD-L1 status, tumor-infiltrating lymphocyte levels, or the neutrophil to lymphocyte ratio. But patients with a high tumor mutational burden had a numerically better PFS with pembrolizumab plus eribulin than those given eribulin alone.
Grade 3–4 adverse events occurred in 68% of the combination arm and 61% of the eribulin monotherapy arm, most frequently neutropenia (37% in both), febrile neutropenia (9 vs 14%), and liver enzyme elevation (14 vs 7%).
Liver enzyme elevation and rash were the most common potentially immune-related adverse events in the pembrolizumab–eribulin group, experienced by 39% and 30% of patients, respectively. And two patients died after developing immune-related colitis, neutropenia, and sepsis.
“It remains unclear if the lack of benefit in this trial is due to the disease subtype, pretreated population, inclusion of patients with PD-L1–negative tumors, or choice of chemotherapy backbone,” say the researchers.
“Further efforts to explore the benefits of adding checkpoint inhibition to chemotherapy in HR-positive, [HER2]-negative disease are needed, specifically trials powered to assess efficacy in patients with PD-L1–positive tumors and focused on less heavily pretreated patients,” they conclude.
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JAMA Oncol 2020; doi:10.1001/jamaoncol.2020.3524