• Janice M Mehnert, Emily Bergsland, Bert H O'Neil, Armando Santoro, SchellensJan H MJHMNetherlands Cancer Institute, Amsterdam, The Netherlands.Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands., Roger B Cohen, Toshihiko Doi, Patrick A Ott, Michael J Pishvaian, Igor Puzanov, Kyaw L Aung, Chiun Hsu, Christophe Le Tourneau, Antoine Hollebecque, Elena Élez, Kenji Tamura, Marlena Gould, Ping Yang, Karen Stein, and Sarina A Piha-Paul.
• Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
• Cancer. 2020 Jul 1; 126 (13): 3021-3030.

BackgroundDespite 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.MethodsPatients 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.ResultsOf 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).ConclusionsPembrolizumab demonstrated antitumor activity in a subset of patients with NETs and was well-tolerated.© 2020 American Cancer Society.

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