In a phase II trial reported in JAMA Oncology, Sara M. Tolaney, MD, MPH, and colleagues found that the addition of pembrolizumab to eribulin did not improve progression-free survival in women with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer.

As stated by the investigators, “Prior studies have shown that only a small proportion of patients with HR-positive metastatic breast cancer experience benefit from PD-1/ PD-L1 inhibitors given as monotherapy. There are data suggesting that activity may be greater with combination strategies.”

Sara M. Tolaney, MD, MPH

Study Details

The open-label trial included 88 patients (intent-to-treat population) from Dana-Farber Cancer Institute, Massachusetts General Hospital, and Beth Israel Deaconess Medical Center who had received two or more lines of hormonal therapy and none to two lines of chemotherapy. Individuals were randomly assigned between April 2017 and August 2018 to receive eribulin at 1.4 mg/m² on days 1 and 8 plus pembrolizumab at 200 mg on day 1 of 21-day cycles (n = 44) or eribulin alone (n = 44).

At the time of disease progression, patients in the eribulin monotherapy group were permitted to cross over to pembrolizumab monotherapy. The primary endpoint was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1.

Progression-Free Survival and Secondary Endpoints

Median follow-up at data cutoff was 10.5 months (95% confidence interval [CI] = 0.4–22.8 months). Median progression-free survival was 4.1 months in the combination group vs 4.2 months in the eribulin group (hazard ratio [HR] = 0.80, 95% CI = 0.50–1.26; P = .33).

Testing in 65 patients showed PD-L1–positive disease in 24. Among 13 vs 11 patients with PD-L1–positive disease, median progression-free survival was 4.2 months vs 4.3 months (HR = 0.84, 95% CI = 0.35–2.00; P = .69). Additional analyses indicated that tumor-infiltrating lymphocytes, tumor mutational burden, and genomic alterations were not associated with progression-free survival.

The objective response rates (all partial responses) were 27% in the combination group vs 34% in the eribulin group (P = .49). Median durations of response were 1.5 months (range = 0–13.6 months) vs 2.1 months (range = 0.2–4.6 months).

Crossover treatment with pembrolizumab was initiated in 14 patients from the eribulin group, with 1 experiencing stable disease.

Overall survival data were not mature at the time of analysis. Based on available survival data, median overall survival was 13.4 months in the combination group vs 12.5 months in the eribulin group (HR = 0.87, 95% CI = 0.48–1.59; P = .65). Among patients with PD-L1–positive disease, median durations were 10.4 vs 13.1 months (HR = 1.59, 95% CI = 0.50–5.06; P = .43).

Adverse Events

Grade 3 or 4 adverse events occurred in 68% of the combination group vs 61% of the eribulin group, with the most common being neutropenia (37% in both groups), febrile neutropenia (9% vs 14%), and liver enzyme elevation (14% vs 7%). The most common potentially immune-related adverse events of any grade in the combination group were elevated liver enzymes (39%), rash (30%), and hypothyroidism (14%). Treatment-related death occurred in two patients in the combination group, both due to immune-related colitis, neutropenia, and sepsis attributed to both drugs.

The investigators concluded, “In this randomized clinical trial of patients with HR-positive, [HER2]-negative metastatic breast cancer, the addition of pembrolizumab to eribulin did not improve progression-free survival, objective response rate, or overall survival compared with eribulin alone in either the intention-to-treat or PD-L1–positive populations. Further efforts to explore the benefits of adding checkpoint inhibition to chemotherapy among less heavily pretreated patients are needed.”

Dr. Tolaney, of Dana-Farber Cancer Institute, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was funded by Merck & Co. For full disclosures of the study authors, visit jamanetwork.com.