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Targeted Oncology

, Volume 13, Issue 3, pp 409–416 | Cite as

Avelumab: A Review in Metastatic Merkel Cell Carcinoma

Adis Drug Evaluation

Abstract

Avelumab (Bavencio®) is a fully human IgG1 monoclonal antibody that is directed against programmed cell death ligand 1 (PD-L1). Avelumab functions as an immune checkpoint inhibitor and has recently been approved in the USA, the EU and Japan for the treatment of metastatic Merkel cell carcinoma (MCC). It is thus the first therapeutic agent specifically approved for use in this indication, and is approved for use independent of line of treatment. Approval for avelumab in metastatic MCC was based on the two-part, single-arm, phase II trial, JAVELIN Merkel 200. In Part A of the study, confirmed objective responses were observed in approximately one-third of patients with chemotherapy-refractory metastatic MCC treated with avelumab. The responses were observed early and appeared to be durable, with an estimated 74% of responses having a duration ≥ 12 months. Furthermore, interim results from a separate cohort of patients (Part B) indicate an objective response rate for avelumab of > 60% in patients who were chemotherapy-naïve in the metastatic disease setting. Avelumab is associated with a risk of immune-related adverse events but, overall, has an acceptable and manageable safety and tolerability profile. In conclusion, currently available data suggest that avelumab presents a clinically beneficial new treatment option for metastatic MCC, a rare but aggressive cancer associated with a poor prognosis.

Notes

Acknowledgements

During the peer review process, the manufacturer of avelumab was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Compliance with Ethical Standards

Funding

The preparation of this review was not supported by any external funding.

Conflicts of Interest

Matt Shirley is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

References

  1. 1.
    Schadendorf D, Lebbe C, zur Hausen A, et al. Merkel cell carcinoma: epidemiology, prognosis, therapy and unmet medical needs. Eur J Cancer. 2017;71:53–69.CrossRefPubMedGoogle Scholar
  2. 2.
    Amaral T, Leiter U, Garbe C. Merkel cell carcinoma: epidemiology, pathogenesis, diagnosis and therapy. Rev Endocr Metab Disord. 2017;18(4):517–32.CrossRefPubMedGoogle Scholar
  3. 3.
    Becker JC, Stang A, DeCaprio JA, et al. Merkel cell carcinoma. Nat Rev Dis Primers. 2017;3:17077.CrossRefPubMedGoogle Scholar
  4. 4.
    Harms KL, Healy MA, Nghiem P, et al. Analysis of prognostic factors from 9387 Merkel cell carcinoma cases forms the basis for the new 8th edition AJCC staging system. Ann Surg Oncol. 2016;23(11):3564–71.CrossRefPubMedGoogle Scholar
  5. 5.
    Cassler NM, Merrill D, Bichakjian CK, et al. Merkel cell carcinoma therapeutic update. Curr Treat Options in Oncol. 2016;17(36)Google Scholar
  6. 6.
    Desch L, Kunstfeld R. Merkel cell carcinoma: chemotherapy and emerging new therapeutic options. J Skin Cancer. 2013;2013:327150.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Lebbe C, Becker JC, Grob J-J, et al. Diagnosis and treatment of Merkel cell carcinoma. European consensus-based interdisciplinary guideline. Eur J Cancer. 2015;51(16):2396–403.CrossRefPubMedGoogle Scholar
  8. 8.
    National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN guidelines®): Merkel cell carcinoma - version 1.2018. 2017. https://www.nccn.org/. Accessed 20 Apr 2018.
  9. 9.
    Nghiem P, Kaufman HL, Bharmal M, et al. Systematic literature review of efficacy, safety and tolerability outcomes of chemotherapy regimens in patients with metastatic Merkel cell carcinoma. Future Oncol. 2017;13(14):1263–79.CrossRefPubMedGoogle Scholar
  10. 10.
    Medina PJ, Adams VR. PD-1 pathway inhibitors: immuno-oncology agents for restoring antitumor immune responses. Pharmacotherapy. 2016;36(3):317–34.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Webb ES, Liu P, Baleeiro R, et al. Immune checkpoint inhibitors in cancer therapy. J Biomed Res. 2017; http://journal.hep.com.cn/jbr/EN/10.7555/JBR.31.20160168#1.
  12. 12.
    Triozzi PL, Fernandez AP. The role of the immune response in Merkel cell carcinoma. Cancers. 2013;5(1):234–54.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Chin K, Chand VK, Nuyten DSA. Avelumab: clinical trial innovation and collaboration to advance anti-PD-L1 immunotherapy. Ann Oncol. 2017;28(7):1658–66.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Lipson EJ, Vincent JG, Loyo M, et al. PD-L1 expression in the Merkel cell carcinoma microenvironment: association with inflammation, Merkel cell polyomavirus and overall survival. Cancer Immunol Res. 2013;1(1):54–63.CrossRefPubMedGoogle Scholar
  15. 15.
    Afanasiev OK, Yelistratova L, Miller N, et al. Merkel polyomavirus-specific T cells fluctuate with Merkel cell carcinoma burden and express therapeutically targetable PD-1 and Tim-3 exhaustion markers. Clin Cancer Res. 2013;19(19):5351–60.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    European Medicines Agency. Bavencio (avelumab): summary of product characteristics. 2018. http://www.ema.europa.eu. Accessed 20 Apr 2018.
  17. 17.
    US FDA. Bavencio® (avelumab): US prescribing information. 2017. www.fda.gov/. Accessed 20 Apr 2018.
  18. 18.
    Pharmaceuticals and Medical Devices Agency (Japan). Bavencio® (avelumab): Japanese prescribing information. 2017. http://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/380079_4291438A1022_1_01. Accessed 30 Apr 2018.
  19. 19.
    Heery CR, O'Sullivan-Coyne G, Madan RA, et al. Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN solid tumor): a phase 1a, multicohort, dose-escalation trial. Lancet Oncol. 2017;18(5):587–98.CrossRefPubMedGoogle Scholar
  20. 20.
    Boyerinas B, Jochems C, Fantini M, et al. Antibody-dependent cellular cytotoxicity activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells. Cancer Immunol Res. 2015;3(10):1148–57.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Fujii R, Friedman ER, Richards J, et al. Enhanced killing of chordoma cells by antibody-dependent cell-mediated cytotoxicity employing the novel anti-PD-L1 antibody avelumab. Oncotarget. 2016;7(23):33498–511.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Grenga I, Donahue RN, Lepone LM, et al. A fully human IgG1 anti-PD-L1 MAb in an in vitro assay enhances antigen-specific T-cell responses. Clin Transl Immunology. 2016;5(5):e83.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    European Medicines Agency. European public assessment report: Bavencio (avelumab). 2017. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004338/WC500236649.pdf. Accessed 20 Apr 2018.
  24. 24.
    D'Angelo SP, Russell J, Lebbé C, et al. Efficacy and safety of first-line avelumab treatment in patients with stage IV metastatic Merkel cell carcinoma: a preplanned interim analysis of a clinical trial. JAMA Oncol. 2018;  https://doi.org/10.1001/jamaoncol.2018.0077.
  25. 25.
    Kaufman HL, Russell J, Hamid O, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016;17(10):1374–85.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Kaufman HL, Russell JS, Hamid O, et al. Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after ≥1 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial. J Immunother Cancer. 2018;6(1):7.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    D'Angelo SP, Russell JS, Bhatia S, et al. 18-month efficacy and safety update from JAVELIN Merkel 200 part A: a phase II study of avelumab in metastatic Merkel cell carcinoma progressed on chemotherapy [abstract no. 192 plus poster]. J Clin Oncol. 2018;36(Suppl 5S).Google Scholar
  28. 28.
    Kelly K, Infante JR, Taylor MH, et al. Safety profile of avelumab in patients with advanced solid tumors: a pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials. Cancer. 2018;124(9):2010-17.Google Scholar
  29. 29.
    Wang P-F, Chen Y, Song S-Y, et al. Immune-related adverse events associated with anti-PD-1/PD-L1 treatment for malignancies: a meta-analysis. Front Pharmacol. 2017;8:730.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Cowey CL, Mahnke L, Espirito J, et al. Real-world treatment outcomes in patients with metastatic Merkel cell carcinoma treated with chemotherapy in the USA. Future Oncol. 2017;13(19):1699–710.CrossRefPubMedGoogle Scholar
  31. 31.
    Becker JC, Lorenz E, Ugurel S, et al. Evaluation of real-world treatment outcomes in patients with distant metastatic Merkel cell carcinoma following second-line chemotherapy in Europe. Oncotarget. 2017;8(45):79731–41.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Iyer JG, Blom A, Doumani R, et al. Response rates and durability of chemotherapy among 62 patients with metastatic Merkel cell carcinoma. Cancer Med. 2016;5(9):2294–301.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

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