Skip to main content

Advertisement

SpringerLink
Log in

The Landmark Series: Non-melanoma Skin Cancers

  • Melanoma
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Surgery with or without radiation has always been the mainstay of treatment for patients with non-melanoma skin cancers, including basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma. Until recently, there were no effective systemic therapies for patients with advanced disease. This review will focus on the landmark clinical trials that led to Food and Drug Administration (FDA) approval of Vismodegib for advanced basal cell carcinoma (ERIVANCE BCC) and pembrolizumab for advanced Merkel cell carcinoma (KEYNOTE-017). These trials have not only changed the landscape for patients with metastatic disease but also notably for patients with locally advanced disease that is either unresectable or resectable with high morbidity. Additional mention is made for the clinical trial that led to FDA approval of cemiplimab for advanced cutaneous squamous cell carcinoma (EMPOWER-CSCC-1), which is already changing practice patterns, but for which longer-term data are still needed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Fang LC, Lemos B, Douglas J, Iyer J, Nghiem P. Radiation monotherapy as regional treatment for lymph node-positive Merkel cell carcinoma. Cancer. 2010;116(7):1783–90.

    Article  Google Scholar 

  2. Asgari MM, Moffet HH, Ray GT, Quesenberry CP. Trends in basal cell carcinoma incidence and identification of high-risk subgroups, 1998–2012. JAMA Dermatol. 2015;151(9):976–81.

    Article  Google Scholar 

  3. NCCN Clinical Practice Guidelines in Oncology: Basal Cell Skin Cancer (Version 1.2019). 2019. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf. Accessed 5 June 2019.

  4. Caro I, Low JA. The role of the hedgehog signaling pathway in the development of basal cell carcinoma and opportunities for treatment. Clin Cancer Res. 2010;16(13):3335–39.

    Article  CAS  Google Scholar 

  5. Xie J, Murone M, Luoh SM, et al. Activating smoothened mutations in sporadic basal-cell carcinoma. Nature. 1998;391(6662):90–2.

    Article  CAS  Google Scholar 

  6. Gailani MR, Stahle-Backdahl M, Leffell DJ, et al. The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat Gen. 1996;14(1):78–81.

    Article  CAS  Google Scholar 

  7. LoRusso PM, Rudin CM, Reddy JC, et al. Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory, locally advanced or metastatic solid tumors. Clin Cancer Res. 2011;17(8):2502–11.

    Article  CAS  PubMed  Google Scholar 

  8. Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366(23):2171–9.

    Article  CAS  PubMed  Google Scholar 

  9. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.

    Article  CAS  PubMed  Google Scholar 

  10. Graham RA, Lum BL, Cheeti S, et al. Pharmacokinetics of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with locally advanced or metastatic solid tumors: the role of alpha-1-acid glycoprotein binding. Clin Cancer Res. 2011;17(8):2512–20.

    Article  CAS  PubMed  Google Scholar 

  11. Sekulic A, Migden MR, Basset-Seguin N, et al. Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study. BMC Cancer. 2017;17(1):332.

    Article  PubMed  Google Scholar 

  12. Basset-Seguin N, Hauschild A, Kunstfeld R, et al. Vismodegib in patients with advanced basal cell carcinoma: primary analysis of STEVIE, an international, open-label trial. Eur J Cancer. 2017;86:334–48.

    Article  CAS  Google Scholar 

  13. Migden MR, Guminski A, Gutzmer R, et al. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. Lancet Oncol. 2015;16(6):716–28.

    Article  CAS  Google Scholar 

  14. Moeholt K, Aagaard H, Pfeiffer P, Hansen O. Platinum-based cytotoxic therapy in basal cell carcinoma–a review of the literature. Acta Oncol. 1996;35(6):677–82.

    Article  CAS  Google Scholar 

  15. Nghiem P, Kaufman HL, Bharmal M, Mahnke L, Phatak H, Becker JC. 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.

    Article  CAS  PubMed  Google Scholar 

  16. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008;319(5866):1096–100.

    Article  CAS  PubMed  Google Scholar 

  17. Wong SQ, Waldeck K, Vergara IA, et al. UV-associated mutations underlie the etiology of MCV-negative merkel cell carcinomas. Cancer Res. 2015;75(24):5228–34.

    Article  CAS  Google Scholar 

  18. Goh G, Walradt T, Markarov V, et al. Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy. Oncotarget. 2016;7(3):3403–15.

    Article  Google Scholar 

  19. Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–8.

    Article  CAS  PubMed  Google Scholar 

  20. Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20.

    Article  CAS  PubMed  Google Scholar 

  21. Nghiem PT, Bhatia S, Lipson EJ, et al. PD-1 Blockade with pembrolizumab in advanced Merkel-cell carcinoma. N Engl J Med. 2016;374(26):2542–52.

    Article  CAS  PubMed  Google Scholar 

  22. Nghiem P, Bhatia S, Lipson EJ, et al. Durable tumor regression and overall survival in patients with advanced merkel cell carcinoma receiving pembrolizumab as first-line therapy. J Clin Oncol. 2019;37(9):693–702.

    Article  CAS  Google Scholar 

  23. Sun X, Roudi R, Dai T, et al. Immune-related adverse events associated with programmed cell death protein-1 and programmed cell death ligand 1 inhibitors for non-small cell lung cancer: a PRISMA systematic review and meta-analysis. BMC Cancer. 2019;19(1):558.

    Article  PubMed  Google Scholar 

  24. 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.

    Article  CAS  PubMed  Google Scholar 

  25. D’Angelo SP, Russell J, Lebbe 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;4(9):e180077.

    Article  PubMed  Google Scholar 

  26. Voog E, Biron P, Martin JP, Blay JY. Chemotherapy for patients with locally advanced or metastatic Merkel cell carcinoma. Cancer. 1999;85(12):2589–95.

    Article  CAS  Google Scholar 

  27. NCCN Clinical Practice Guidelines in Oncology: Merkel Cell Carcinoma (version 2.2019). 18 Jan 2019; 2019.

  28. Migden MR, Rischin D, Schmults CD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med. 2018;379(4):341–51.

    Article  CAS  Google Scholar 

  29. Khansur T, Kennedy A. Cisplatin and 5-fluorouracil for advanced locoregional and metastatic squamous cell carcinoma of the skin. Cancer. 1991;67(8):2030–2.

    Article  CAS  Google Scholar 

  30. Guthrie TH, Jr., Porubsky ES, Luxenberg MN, Shah KJ, Wurtz KL, Watson PR. Cisplatin-based chemotherapy in advanced basal and squamous cell carcinomas of the skin: results in 28 patients including 13 patients receiving multimodality therapy. J Clin Oncol. 1990;8(2):342–6.

    Article  Google Scholar 

  31. Nakamura K, Okuyama R, Saida T, Uhara H. Platinum and anthracycline therapy for advanced cutaneous squamous cell carcinoma. Int J Clin Oncol. 2013;18(3):506–9.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, NYU Langone Health, New York, NY, USA

    Ann Y. Lee MD & Russell S. Berman MD

Authors
  1. Ann Y. Lee MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Russell S. Berman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ann Y. Lee MD.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, A.Y., Berman, R.S. The Landmark Series: Non-melanoma Skin Cancers. Ann Surg Oncol 27, 22–27 (2020). https://doi.org/10.1245/s10434-019-07831-9

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-019-07831-9

Search

Navigation