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Clinical Trial
. 2020 Apr;122(9):1309-1314.
doi: 10.1038/s41416-020-0775-0. Epub 2020 Mar 10.

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

Namrata Vijayvergia #  1 , Arvind Dasari #  2 , Mengying Deng  3 , Samuel Litwin  3 , Taymeyah Al-Toubah  4 , R Katherine Alpaugh  3 , Efrat Dotan  3 , Michael J Hall  3 , Nicole M Ross  3 , Melissa M Runyen  3 , Crystal S Denlinger  3 , Daniel M Halperin  2 , Steven J Cohen  5 , Paul F Engstrom  3 , Jonathan R Strosberg  4
Affiliations
Clinical Trial

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

Namrata Vijayvergia et al. Br J Cancer. 2020 Apr.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1. Waterfall plot depicting best overall response to therapy by patient.
Five patients were not evaluable for response. # represents patients who progressed due to appearance of new lesions despite reduction or less than 20% increase in tumor size. PD progressive disease, SD stable disease, PR partial response.
Fig. 2
Fig. 2. Kaplan-Meier curve showing progression free survival (PFS) among 29 patients who received Pembrolizumab.
Median PFS 8.86 weeks (95% confidence interval 6.00–9.43).
Fig. 3
Fig. 3. Kaplan Meier curve showing overall survival since treatment initiation among 29 patients who received Pembrolizumab.
Medial overall survival was 20.43 weeks (95% confidence interval 12.86- not estimated).
See this image and copyright information in PMC

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