Pembrolizumab for the treatment of programmed death–ligand 1‒positive advanced carcinoid or pancreatic neuroendocrine tumors: Results from the KEYNOTE-028 study

Janice M. Mehnert, Emily Bergsland, Bert H. O’Neil, Armando Santoro, Jan H.M. Schellens, 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, Sarina A. Piha-Paul

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Background: 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 ( 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. Methods: 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. Results: 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). Conclusions: Pembrolizumab demonstrated antitumor activity in a subset of patients with NETs and was well-tolerated.

Original languageEnglish (US)
Pages (from-to)3021-3030
Number of pages10
Issue number13
StatePublished - Jul 1 2020
Externally publishedYes


  • KEYNOTE-028
  • antitumor activity
  • carcinoid tumors
  • immunotherapy
  • pancreatic neuroendocrine tumors
  • pembrolizumab
  • programmed death–ligand 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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