Results from a phase Ib trial suggest that the programmed death 1 (PD-1) inhibitor pembrolizumab has activity and an acceptable toxicity profile as single-agent therapy in heavily pretreated, advanced triple-negative breast cancer (TNBC).
“TNBC tumors are frequently of high histological grade, present at an advanced stage, are typically more aggressive and difficult to treat than hormone receptor–positive tumors, and are associated with a higher risk of early relapse,” wrote study authors led by Rita Nanda, MD, of the University of Chicago. “Given the suboptimal outcomes with chemotherapy, new targeted therapies for TNBC are urgently needed.”
Previous research has suggested that immunotherapy may provide benefit in TNBC. The new study, called KEYNOTE-012, was a nonrandomized phase Ib trial of pembrolizumab, which included a number of malignancies; this analysis focused on the 32 TNBC patients who were positive for the PD-1 ligand PD-L1. The results were published in the Journal of Clinical Oncology.
This was a heavily pretreated population, with 46.9% of patients having received at least three lines of therapy for metastatic disease, and 25.0% having received at least five lines. The median age in the study was 50.5 years.
Of the 32 patients included, 37.5% experienced some decrease in tumor burden from baseline. Twenty-seven of the patients met protocol-specified inclusion criteria for the efficacy analysis, and in those patients the overall response rate was 18.5%. One patient (3.7%) had a complete response, four had a partial response (14.8%), seven had stable disease (25.9%), and 13 patients had progressive disease (48.1%). The overall disease control rate (complete or partial response or stable disease for at least 24 weeks) was 25.9%.
Most patients (56.3%) experienced some treatment-related toxicity, and 15.6% had at least one grade 3 or higher adverse event (AE). The most common treatment-related AEs were arthralgia (18.8%), fatigue (18.8%), myalgia (18.8%), and nausea (15.6%). The grade 3 AEs included anemia, aseptic meningitis, lymphopenia, headache, and pyrexia. One patient died due to a treatment-related AE, a combination of disseminated intravascular coagulation and grade 4 decreased blood fibrinogen. Onset of this event occurred 10 days after the initial pembrolizumab dose.
The authors found that there was evidence of increasing probability of response with pembrolizumab with increasing expression of PD-L1, but they noted the small population size limits that finding’s significance. The 18.5% overall response rate was similar to other subsets of the KEYNOTE-012 study, including head and neck cancer patients (21.4%) and gastric cancer patients (22.2%).
“Overall, these results support further development of pembrolizumab for the treatment of metastatic TNBC,” the authors concluded. A phase II trial (KEYNOTE-086) is currently enrolling TNBC patients to test this therapy, and other studies that will combine the PD-1 inhibitor with other therapies are also in development.