As reported in the British Journal of Cancer by Namrata Vijayvergia, MD, and colleagues, a pooled analysis of two phase II studies found that pembrolizumab monotherapy showed little activity in patients with previously treated metastatic high-grade neuroendocrine neoplasms.

Namrata Vijayvergia, MD

Study Details

In the two studies, 29 patients with metastatic high-grade disease (Ki-67 proliferative index > 20%) that progressed after at least one line of prior therapy were enrolled between November 2016 and May 2018. Patients were treated with 200 mg of pembrolizumab every 3 weeks. Overall, 97% of patients had received prior platinum therapy and 45% had received one prior line of therapy. Overall, primary tumors were gastrointestinal in 48% and pancreatic in 34%.

Treatment Outcomes  

Objective response (partial response) was observed in one patient (3.4%) and an additional six patients (20.7%) had stable disease, yielding a disease control rate of 24.1%. Disease control was maintained at 18 weeks in three patients (10.3%); the patient with partial response was still experiencing ongoing response at 13 months. Median progression-free survival was 8.9 weeks and median overall survival was 20.4 weeks. For programmed cell death ligand 1 (PD-L1)-positive (47% of patients with available data) vs PD-L1–negative patients, there were no differences in disease control rate (P = .56), progression-free survival (P = .88), or overall survival (P = .055).  

Adverse Events

Treatment-related grade 3 adverse events occurred in nine patients (31%), with the most common being increased alkaline phosphatase (10%) and increased aspartate aminotransferase (10%). No grade 4 treatment-related adverse events were observed.

As noted by the investigators, “Despite prior evidence of activity of [immune checkpoint inhibitor] immunotherapy in neuroendocrine cancers originating in the lung and skin, limited evidence of activity with pembrolizumab was observed in this combined analysis of [high-grade neuroendocrine neoplasms] originating in other organs.”

They concluded: “Pembrolizumab can be safely administered to patients with [high-grade neuroendocrine neoplasms] but has limited activity as a single agent. Successful completion of our trials suggest studies in [high-grade neuroendocrine neoplasms] are feasible and present an unmet need. Further research to identify active combination therapies should be considered.”

Dr. Vijayvergia, of Fox Chase Cancer Center, is the corresponding author for the British Journal of Cancer article.

Disclosure: The study was supported by Merck and by a grant from the National Cancer Institute. For full disclosures of the study authors, visit nature.com.