Despite a protracted disease course and multiple available therapies, patients with well‐differentiated neuroendocrine tumors (NETs) inevitably experience disease progression. Programmed death–ligand 1 (PD‐L1) has been associated with NET progression and prognosis. The multicohort, phase 1 KEYNOTE‐028 study (ClinicalTrials.gov identifier NCT02054806) evaluated the activity and safety of the anti–programmed cell death protein 1 immunotherapy pembrolizumab in patients with well‐differentiated or moderately‐differentiated NETs.

Patients with PD‐L1–positive, locally advanced or metastatic carcinoid or well–differentiated or moderately‐differentiated pancreatic NETs (pNETs) were enrolled into separate cohorts and received pembrolizumab at a dose of 10 mg/kg every 2 weeks for up to 2 years. The objective response rate was the primary endpoint (as per Response Evaluation Criteria in Solid Tumors version 1.1, by investigator review). Safety was a secondary endpoint.

Of 170 and 106 patients, respectively, who had evaluable samples among those screened for the carcinoid and pNET cohorts, 21% and 25%, respectively, had PD‐L1–positive tumors; of these, 25 and 16 patients, respectively, were eligible and treated. The median follow‐up was 20 months (range, 2‐35 months) and 21 months (range, 5‐32 months), respectively. The objective response rate was 12.0% (95% CI, 2.5%‐31.2%) and 6.3% (95% CI, 0.2%‐30.2%), respectively; 3 partial responses occurred among the carcinoid cohort and 1 among the pNET cohort. The median duration of response in the carcinoid cohort was 9.2 months (range, 6.9‐11.1 months), and was not reached in the pNET cohort. No complete responses occurred. Treatment‐related adverse events occurred in 68% and 69% of patients, respectively, most often diarrhea (7 patients in the carcinoid cohort and 4 patients in the pNET cohort) and fatigue (6 patients in each cohort). Hypothyroidism was the most common immune‐mediated adverse event (5 patients in the carcinoid cohort and 2 patients in the pNET cohort).

Pembrolizumab demonstrated antitumor activity in a subset of patients with NETs and was well‐tolerated.