Pembrolizumab for the treatment of programmed death–ligand 1‒positive advanced carcinoid or pancreatic neuroendocrine tumors: Results from the KEYNOTE-028 study - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cancer Année : 2020

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
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Emily K. Bergsland
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Bert H. O’neil
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Armando Santoro
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Jan H.M. Schellens
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Roger B. Cohen
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Toshihiko Doi
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Patrick Alexander Ott
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Michael J. Pishvaian
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Igor Puzanov
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Kyaw L. Aung
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Chiun Hsu
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?lena Élez
Kenji Tamura
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Marlena Gould
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Ping Yang
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Karen Stein
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Sarina Anne Piha-Paul

Résumé

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.
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hal-02927423 , version 1 (01-09-2020)

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Janice M. Mehnert, Emily K. Bergsland, Bert H. O’neil, Armando Santoro, Jan H.M. Schellens, et al.. Pembrolizumab for the treatment of programmed death–ligand 1‒positive advanced carcinoid or pancreatic neuroendocrine tumors: Results from the KEYNOTE-028 study. Cancer, 2020, 126 (13), pp.3021-3030. ⟨10.1002/cncr.32883⟩. ⟨hal-02927423⟩
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