Clinical Study

Pembrolizumab monotherapy in patients with previously treated metastatic high-grade neuroendocrine neoplasms: joint analysis of two prospective, non-randomised trials



Metastatic high-grade neuroendocrine neoplasms (G3NENs) have limited treatment options after progression on platinum-based therapy. We addressed the role of Pembrolizumab in patients with previously treated metastatic G3NENs.


Two open-label, phase 2 studies enrolled patients with G3NEN (Ki-67 > 20%) to receive Pembrolizumab at 200 mg I.V. every 3 weeks. Radiographic evaluation was conducted every 9 weeks with overall response rate as the primary endpoint.


Between November 2016 and May 2018, 29 patients (13 males/16 females) with G3NENs were enrolled. One patient (3.4%) had an objective response and an additional six patients (20.7%) had stable disease, resulting in a disease control rate of 24.1%. Disease control rate (DCR) at 18 weeks was 10.3% (3/29). There was no difference in the DCR, PFS or OS between the PD-L1-negative and -positive groups (p 0.56, 0.88 and 0.55, respectively). Pembrolizumab was well tolerated with only 9 grade 3, and no grade 4 events considered drug-related.


Pembrolizumab can be safely administered to patients with G3NENs but has limited activity as a single agent. Successful completion of our trials suggest studies in G3NENs are feasible and present an unmet need. Further research to identify active combination therapies should be considered.

Clinical trial registration number

NCT02939651 (10/20/2016).

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Fig. 1: Waterfall plot depicting best overall response to therapy by patient.
Fig. 2: Kaplan-Meier curve showing progression free survival (PFS) among 29 patients who received Pembrolizumab.
Fig. 3: Kaplan Meier curve showing overall survival since treatment initiation among 29 patients who received Pembrolizumab.


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We would like to thank all the patients who participated in this study voluntarily. Previous presentations: Abstracts at ASCO annual meeting 2018 and NANETS annual meeting 2018.

Author information




N.V.: Study concepts, study design, data collection and patient recruitment, data analysis and interpretation, quality control of data and algorithms, manuscript preparation/editing and review, figures and tables. A.D.: study concepts, study design, data collection and patient recruitment, data analysis and interpretation, quality control of data and algorithms, manuscript preparation/editing and review. M.D.: statistical analysis, manuscript preparation/editing and review, figures and tables. S.L.: statistical analysis, manuscript review. T.A.: data collection and patient recruitment, manuscript review. R.K.A.: data analysis and interpretation, manuscript review. E.D.: data collection and patient recruitment, manuscript editing/review. M.J.H.: data collection and patient recruitment, manuscript editing/review. N.M.R.: data collection and patient recruitment, manuscript review. M.M.R.: data collection and patient recruitment, manuscript review. C.S.D.: data collection and patient recruitment, manuscript editing/review. D.M.H.: data collection and patient recruitment, manuscript editing/review. S.J.C.: study concept/design, manuscript editing/review. P.F.E.: study concept/design, manuscript editing/review. J.R.S.: study concepts, study design, data collection and patient recruitment, data analysis and interpretation, quality control of data and algorithms, manuscript preparation/editing and review.

Corresponding author

Correspondence to Namrata Vijayvergia.

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Ethics approval and consent to participate

This study has been conducted according to the principles of the declaration of Helsinki 2008. Ethical approval has been granted from Institutional Review Boards at Fox Chase Cancer Center, MD Anderson Cancer Center and H. Lee Moffitt Cancer Center (University of South Florida). All patients signed an informed consent for participating in this trial, including the option of publication of the data.

Consent to publish

Not applicable

Data availability

The data are available for all study authors. The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

N.V.: Research funding from Merck, Bayer. A.D.: Consulting fee from Novartis, Ipsen, Voluntis, Abbvie, Crinetics, Hutchison Pharma and Research funding from Novartis, Eisai, Ipsen, Hutchison Pharma. D.H.: Consulting fee from Lexicon, Ipsen, Advanced Accelarator Applications; Research funding from Genentech, Tarveda, ThermoFisher Scientific. C.D.: Personal fees from Exelixis Astellas, BeiGene, Bayer, Bristol Myer Squibb, Merck, Eli Lilly & Co, EMD Serono; Research funding from Merrimack Pharmaceuticals, Advaxis, Astra Zeneca, Eli Lilly & Co, Roche/Genentech, Amgen, Sanofi Aventis, BeiGene, Lycera, Macrogenics, Agios Pharmaceuticals, Zymeworks, outside the submitted work. M.J.H.: Research funding from Merck, Astra Zeneca. E.D.: Honararia from Pfizer, Boston Medical; Consulting fee from ARMO Biosciences; Research funding from Pfizer, Bayer, Boston Biomedical, Merck, Medimmune, GSK and Eli Lilly Co. J.S.: Consultant fee from Novartis, Speakers bureau for Lexicon and Ipsen.

Funding information

The study was supported by research grant MISP# 53956 from Merck, and NCI Comprehensive Cancer Center Support Grant CA06927.

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Vijayvergia, N., Dasari, A., Deng, M. et al. Pembrolizumab monotherapy in patients with previously treated metastatic high-grade neuroendocrine neoplasms: joint analysis of two prospective, non-randomised trials. Br J Cancer 122, 1309–1314 (2020).

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