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Pembrolizumab and concurrent hypo-fractionated radiotherapy for advanced non-resectable cutaneous squamous cell carcinoma

  • Therapy
  • Published:
European Journal of Dermatology

Abstract

Background

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent non-melanoma skin cancer. Treatment options for inoperable advanced cSCC cases are limited. The efficacy of anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAb) has been reported recently in some patients with cSCC.

Objectives

To evaluate the efficacy of anti-PD-1 mAb in a case series of inoperable advanced cSCC and to analyse the efficacy of concurrent radiotherapy.

Materials and Methods

We retrospectively analysed the files of all patients with advanced inoperable cSCC treated with anti-PD-1 mAb and concurrent radiotherapy outside clinical trials in our skin cancer centre before December 31, 2017.

Results

A total of four patients with locally or regionally advanced cSCC were identified. All patients received pembrolizumab at 2 mg/kg every three weeks and concurrent radiotherapy. Two patients who received pembrolizumab as first-line therapy with concurrent radiotherapy (one with skull and leptomeningeal invasion and one with rapidly progressing regional cSCC) had a complete response, allowing treatment discontinuation, without recurrence after a median of 11 months off treatment. All other patients experienced progressive disease. The median progression-free survival and overall survival were 14.4 and 15.6 months, respectively. No toxicity was observed.

Conclusion

There appears to be a place for pembrolizumab as first-line treatment for unresectable or advanced cSCC. Further studies are needed to evaluate concomitant radiotherapy with anti-PD1 antibodies.

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References

  1. Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: management of advanced and high-stage tumors. J Am Acad Dermatol 2018; 78: 249–61.

    Article  Google Scholar 

  2. Foote MC, McGrath M, Guminski A, et al. Phase II study of single-agent panitumumab in patients with incurable cutaneous squamous cell carcinoma. Ann Oncol 2014; 25: 2047–52.

    Article  CAS  Google Scholar 

  3. Schadendorf D, van Akkooi A, Berking C, et al. Melanoma. Lancet 2018; 392: 971–84.

    Article  Google Scholar 

  4. https://www.ema.europa.eu/en/medicines/human/EPAR/keytruda#authorisation-details-section. Accessed 01 March 2019.

  5. Pickering CR, Zhou JH, Lee JJ, et al. Mutational landscape of aggressive cutaneous squamous cell carcinoma. Clin Cancer Res 2014; 20: 6582–92.

    Article  CAS  Google Scholar 

  6. Belai EB, de Oliveira CE, Gasparoto TH, et al. PD-1 blockage delays murine squamous cell carcinoma development. Carcinogenesis 2014; 35: 424–31.

    Article  CAS  Google Scholar 

  7. Blum V, Müller B, Hofer S, et al. Nivolumab for recurrent cutaneous squamous cell carcinoma: three cases. Eur J Dermatol 2018; 28: 78–81.

    PubMed  Google Scholar 

  8. Deinlein T, Lax SF, Schwarz T, Giuffrida R, Schmid-Zalaudek K, Zalaudek I. Rapid response of metastatic cutaneous squamous cell carcinoma to pembrolizumab in a patient with xeroderma pigmentosum: case report and review of the literature. Eur J Cancer 2017; 83: 99–102.

    Article  Google Scholar 

  9. Assam JH, Powell S, Spanos WC. Unresectable cutaneous squamous cell carcinoma of the forehead with MLH1 mutation showing dramatic response to programmed cell death protein 1 inhibitor therapy. Clin Skin Cancer 2016; 1: 26–9.

    Article  Google Scholar 

  10. Borradori L, Sutton B, Shayesteh P, Daniels GA. Rescue therapy with anti-programmed cell death protein 1 inhibitors of advanced cutaneous squamous cell carcinoma and basosquamous carcinoma: preliminary experience in five cases. Br J Dermatol 2016; 175: 1382–6.

    Article  CAS  Google Scholar 

  11. Chang ALS, Kim J, Luciano R, Sullivan-Chang L, Colevas AD. A case report of unresectable cutaneous squamous cell carcinoma responsive to pembrolizumab, a programmed cell death protein 1 inhibitor. JAMA Dermatol 2016; 152: 106–8.

    Article  Google Scholar 

  12. Ravulapati S, Leung C, Poddar N, Tu Y. Immunotherapy in squamous cell skin carcinoma: a game changer? Am J Med 2017; 130: e207–8.

    Article  Google Scholar 

  13. Degache E, Crochet J, Simon N, et al. Major response to pembrolizumab in two patients with locally advanced cutaneous squamous cell carcinoma. J Eur Acad Dermatol Venereol 2018; 32: e257–8.

    Article  CAS  Google Scholar 

  14. Miller DM, Faulkner-Jones BE, Stone JR, Drews RE. Complete pathologic response of metastatic cutaneous squamous cell carcinoma and allograft rejection after treatment with combination immune checkpoint blockade. JAAD Case Rep 2017; 3: 412–5.

    Article  Google Scholar 

  15. Winkler JK, Schneiderbauer R, Bender C, et al. Anti-programmed cell death-1 therapy in non-melanoma skin cancer. Br J Dermatol 2017; 176: 498–502.

    Article  CAS  Google Scholar 

  16. Chen A, Ali N, Boasberg P, Ho AS. Clinical remission of cutaneous squamous cell carcinoma of the auricle with cetuximab and nivolumab. J Clin Med 2018; 7: 1.

    Google Scholar 

  17. Stevenson ML, Wang CQF, Abikhair M, et al. Expression of programmed cell death ligand in cutaneous squamous cell carcinoma and treatment of locally advanced disease with pembrolizumab. JAMA Dermatol 2017; 153: 299–303.

    Article  Google Scholar 

  18. De Wolf K, Kruse V, Sundahl N, et al. A phase II trial of stereotactic body radiotherapy with concurrent anti-PD1 treatment in metastatic melanoma: evaluation of clinical and immunologic response. J Transl Med 2017; 15: 21.

    Article  Google Scholar 

  19. 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: 341–51.

    Article  CAS  Google Scholar 

  20. Roger A, Finet A, Boru B, et al. Efficacy of combined hypo-fractionated radiotherapy and anti-PD-1 monotherapy in difficult-to-treat advanced melanoma patients. Oncoimmunology 2018; 7: e1442166.

    Article  Google Scholar 

  21. World Medical Association Declaration of Helsinki:. ethical principles for medical research involving human subjects. JAMA 2013; 310: 2191–4.

    Article  Google Scholar 

  22. Sharabi AB, Nirschl CJ, Kochel CM, et al. Stereotactic radiation therapy augments antigen-specific PD-1-mediated antitumor immune responses via cross-presentation of tumor antigen. Cancer Immunol Res 2015; 3: 345–55.

    Article  CAS  Google Scholar 

  23. Rodriguez-Ruiz ME, Vanpouille-Box C, Melero I, Formenti SC, Demaria S. Immunological mechanisms responsible for radiation-induced abscopal effect. Trends Immunol 2018; 39: 644–55.

    Article  CAS  Google Scholar 

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Acknowledgments and disclosures

Acknowledgments: We thank Blandine Boru for the RECIST 1.1 evaluations. Financial support: none. Conflicts of interest: Christine Longvert has received honoraria and non-financial support from MSD (Merck Sharp & Dohme). Astrid Blom and Elisa Funck-Brentano have received an invitation to a Congress from MSD. Philippe Saiag has received consulting fees and travel grants from MSD. The other authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of General and Oncologic Dermatology, Ambroise-Paré hospital, APHP & Research unit EA 4340, university of Versailles-Saint-Quentin-en-Yvelines, Paris-Saclay University, Boulogne-Billancourt, France

    Justine Lavaud, Astrid Blom, Christine Longvert, Magali Fort, Elisa Funck-Brentano & Philippe Saiag

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  1. Justine Lavaud
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  2. Astrid Blom
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  3. Christine Longvert
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  4. Magali Fort
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  5. Elisa Funck-Brentano
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  6. Philippe Saiag
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Corresponding author

Correspondence to Philippe Saiag.

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Lavaud, J., Blom, A., Longvert, C. et al. Pembrolizumab and concurrent hypo-fractionated radiotherapy for advanced non-resectable cutaneous squamous cell carcinoma. Eur J Dermatol 29, 636–640 (2019). https://doi.org/10.1684/ejd.2019.3671

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  • DOI: https://doi.org/10.1684/ejd.2019.3671

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