TY - JOUR
T1 - Pembrolizumab for the treatment of programmed death–ligand 1‒positive advanced carcinoid or pancreatic neuroendocrine tumors
T2 - Results from the KEYNOTE-028 study
AU - Mehnert, Janice M.
AU - Bergsland, Emily
AU - O’Neil, Bert H.
AU - Santoro, Armando
AU - Schellens, Jan H.M.
AU - Cohen, Roger B.
AU - Doi, Toshihiko
AU - Ott, Patrick A.
AU - Pishvaian, Michael J.
AU - Puzanov, Igor
AU - Aung, Kyaw L.
AU - Hsu, Chiun
AU - Le Tourneau, Christophe
AU - Hollebecque, Antoine
AU - Élez, Elena
AU - Tamura, Kenji
AU - Gould, Marlena
AU - Yang, Ping
AU - Stein, Karen
AU - Piha-Paul, Sarina A.
N1 - Funding Information:
Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD). Study management support was provided by Pradeep Thanigaimani, BS, of MSD, and additional statistical support was provided by Chao Gao, PhD, formerly of MSD and funded by MSD. Additional study support was provided by Melanie Leiby, PhD, of MSD, and Jennifer Smedberg, an employee of ExecuPharm on assignment to Merck. Medical writing and editorial assistance was provided by Sheri Arndt, PharmD, of C4 MedSolutions LLC (Yardley, PA), a CHC Group company. This assistance was funded by MSD.
Publisher Copyright:
© 2020 American Cancer Society
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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 (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. 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.
AB - 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 (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. 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.
KW - KEYNOTE-028
KW - antitumor activity
KW - carcinoid tumors
KW - immunotherapy
KW - pancreatic neuroendocrine tumors
KW - pembrolizumab
KW - programmed death–ligand 1
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U2 - 10.1002/cncr.32883
DO - 10.1002/cncr.32883
M3 - Article
C2 - 32320048
AN - SCOPUS:85083807681
SN - 0008-543X
VL - 126
SP - 3021
EP - 3030
JO - Cancer
JF - Cancer
IS - 13
ER -