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Primary cemiplimab treatment for orbital squamous cell carcinoma is effective and may alleviate the need for orbital exenteration

Eye (2023)Cite this article

Subjects

Abstract

Purpose

To evaluate the effectiveness of cemiplimab, a Programmed-cell-death-1(PD-1) protein inhibitor, for the treatment of cutaneous periocular-locally-advanced squamous-cell-carcinoma (POLA-SCC) with orbital-invasion.

Methods

Multicentre real-world retrospective study. Demographic and clinical data were collected and analysed for patients with biopsy-proven POLA-SCC(AJCC-T4) with orbital-invasion who were treated with cemiplimab at one of four tertiary medical centres in 2019–2022.

Results

The cohort included 13 patients, 8 males and 5 females, of median age 76 years (IQR65–86). The median duration of treatment was 5.0months (IQR3.5–10.5) and the median follow-up time, 15.0 months (IQR10.5–30). The overall response rate was 69.2%. Complete response was documented in seven patients (53.8%), partial response in two (15.4%), stable disease in one (7.7%), and progressive disease in two (15.4%); in one patient (7.7%), response was not evaluable. Six complete responders (46.1% of the cohort) received no further treatment and did not have a recurrence during an average follow-up of 6.14 (±6.9) months from treatment cessation. None of the patients underwent orbital-exenteration. The majority of adverse events were mild (grade-1), except for a moderate increase in creatinine level (grade-2), severe bullous dermatitis (grade-3), and myocarditis (grade-5) in one patient each. Four patients (30.7%) died during the follow-up period, all of whom had an Eastern-Cooperative-Oncology-Group score of 4 at presentation.

Conclusions

To our knowledge, this is the largest study to date on cemiplimab therapy for cutaneous POLA-SCC with orbital-invasion. Treatment was shown to be effective, with an overall response rate of 69.2%. Cemiplimab holds promise for the treatment of patients with tumours invading the orbit as it may alleviate the need for orbital exenteration.

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Fig. 1: Treatment timeline and follow-up of each of the 13 patients with locally advanced squamous cell carcinoma treated with cemiplimab.
Fig. 2: MRI scans of an 82-year-old man with squamous cell carcinoma with orbital involvement.

Data availability

The data that support the findings of this study are not openly available due to the hospital’s patient privacy policy. The patient shown in Supplementary Fig. 1 has provided written consent for their image to be used in published media.

References

  1. Reifler DM, Hornblass A. Squamous cell carcinoma of the eyelid. Surv Ophthalmol. 1986;30:349–65.

    Article  CAS  Google Scholar 

  2. Donaldson MJ, Sullivan TJ, Whitehead KJ, Williamson RM. Squamous cell carcinoma of the eyelids. Br J Ophthalmol. 2002;86:1161–5.

    Article  CAS  Google Scholar 

  3. Nemet AY, Deckel Y, Martin PA, Kourt G, Chilov M, Sharma V, et al. Management of periocular basal and squamous cell carcinoma: a series of 485 cases. Am J Ophthalmol. 2006;142:293–7.

    Article  Google Scholar 

  4. Nasser QJ, Roth KG, Warneke CL, Yin VT, El Sawy T, Esmaeli B. Impact of AJCC ‘T’ designation on risk of regional lymph node metastasis in patients with squamous carcinoma of the eyelid. Br J Ophthalmol. 2014;98:498–501.

    Article  Google Scholar 

  5. Sun MT, Andrew NH, O’Donnell B, McNab A, Huilgol SC, Selva D. Periocular squamous cell carcinoma: TNM staging and recurrence. Ophthalmology. 2015;122:1512–6.

    Article  Google Scholar 

  6. Goldfarb JA, Ferrarotto R, Gross N, Goepfert R, Debnam JM, Gunn B, et al. Immune checkpoint inhibitors for treatment of periorbital squamous cell carcinoma. Br J Ophthalmol. 2021; https://doi.org/10.1136/bjophthalmol-2021-319417.

  7. Malhotra R, Huilgol SC, Huynh NT, Selva D. The Australian Mohs database: periocular squamous cell carcinoma. Ophthalmology. 2004;111:617–23.

    Article  Google Scholar 

  8. Faustina M, Diba R, Ahmadi MA, Esmaeli B. Patterns of regional and distant metastasis in patients with eyelid and periocular squamous cell carcinoma. Ophthalmology. 2004;111:1930–2.

    Article  Google Scholar 

  9. Ridenhour CE, Spratt JS Jr. Epidermoid carcinoma of the skin involving the parotid gland. Am J Surg. 1966;112:504–7.

    Article  CAS  Google Scholar 

  10. Sullivan TJ. Squamous cell carcinoma of eyelid, periocular, and periorbital skin. Int Ophthalmol Clin. 2009;49:17–24.

    Article  Google Scholar 

  11. McCord CD Jr, Cavanagh HD. Microscopic features and biologic behavior of eyelid tumors. Ophthalmic Surg. 1980;11:671–81.

    Google Scholar 

  12. Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol. 1992;26:976–90.

    Article  CAS  Google Scholar 

  13. Yin VT, Pfeiffer ML, Esmaeli B. Targeted therapy for orbital and periocular basal cell carcinoma and squamous cell carcinoma. Ophthalmic Plast Reconstr Surg. 2013;29:87–92.

    Article  Google Scholar 

  14. Xu S, Sagiv O, Rubin ML, Sa HS, Tetzlaff MT, Nagarajan P, et al. Validation study of the AJCC cancer staging manual, eighth edition, staging system for eyelid and periocular squamous cell carcinoma. JAMA Ophthalmol. 2019;137:537–42.

    Article  Google Scholar 

  15. Lazarevic D, Ramelyte E, Dummer R, Imhof L. Radiotherapy in periocular cutaneous malignancies: a retrospective study. Dermatology. 2019;235:234–9.

    Article  Google Scholar 

  16. Fitzpatrick PJ, Thompson GA, Easterbrook WM, Gallie BL, Payne DG. Basal and squamous cell carcinoma of the eyelids and their treatment by radiotherapy. Int J Radiat Oncol Biol Phys. 1984;10:449–54.

    Article  CAS  Google Scholar 

  17. Gerring RC, Ott CT, Curry JM, Sargi ZB, Wester ST. Orbital exenteration for advanced periorbital non-melanoma skin cancer: prognostic factors and survival. Eye. 2017;31:379–88.

    Article  CAS  Google Scholar 

  18. Rasmussen ML, Ekholm O, Prause JU, Toft PB. Quality of life of eye amputated patients. Acta Ophthalmol. 2012;90:435–40.

    Article  Google Scholar 

  19. Ye J, Lou L, Jin K, Xu Y, Ye X, Moss T, et al. Vision-related quality of life and appearance concerns are associated with anxiety and depression after eye enucleation: a cross-sectional study. PLoS One. 2015;10:e0136460.

    Article  Google Scholar 

  20. Baum SH, Pfortner R, Manthey A, Bechrakis NE, Mohr C. Periorbital, conjunctival and primary intraorbital carcinomas: Survival and risk factors after orbital exenteration. Eye. 2021;35:1365–76.

    Article  Google Scholar 

  21. Martel A, Baillif S, Nahon-Esteve S, Gastaud L, Bertolotto C, Lassalle S, et al. Orbital exenteration: an updated review with perspectives. Surv Ophthalmol. 2021;66:856–76.

    Article  Google Scholar 

  22. Kiratli H, Koc I. Orbital exenteration: Institutional review of evolving trends in indications and rehabilitation techniques. Orbit. 2018;37:179–86.

    Article  Google Scholar 

  23. Markham A, Duggan S. Cemiplimab: first global approval. Drugs. 2018;78:1841–6.

    Article  CAS  Google Scholar 

  24. Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, 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 

  25. Schaffer M, Simonovich A, I O, Batash R, Asna N. Use of cemiplimab in locally advanced cutaneous squamous cell carcinoma. J Clin Case Rep. 2020;10:1320.

  26. Migden MR, Khushalani NI, Chang ALS, Lewis KD, Schmults CD, Hernandez-Aya L, et al. Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. Lancet Oncol. 2020;21:294–305.

    Article  CAS  Google Scholar 

  27. Nageli M, Mangana J, Chaloupka K, Dummer R. Cutaneous SCC with orbital invasion: case series. J Eur Acad Dermatol Venereol. 2022;36:59–62.

    Article  Google Scholar 

  28. McLean LS, Lim AM, Webb A, Cavanagh K, Thai A, Magarey M, et al. Immunotherapy to avoid orbital exenteration in patients with cutaneous squamous cell carcinoma. Front Oncol. 2021;11:796197.

    Article  Google Scholar 

  29. Steren B, Burtness B, Bhatia A, Demirci H, Shinder R, Yoo D, et al. Cemiplimab for orbital squamous cell carcinoma in 11 cases. Ophthalmic Plast Reconstr Surg. 2022;38:496–502.

  30. Strippoli S, Fanizzi A, Quaresmini D, Nardone A, Armenio A, Figliuolo F, et al. Cemiplimab in an elderly frail population of patients with locally advanced or metastatic cutaneous squamous cell carcinoma: a single-center real-life experience from Italy. Front Oncol. 2021;11:686308.

    Article  Google Scholar 

  31. Salzmann M, Leiter U, Loquai C, Zimmer L, Ugurel S, Gutzmer R, et al. Programmed cell death protein 1 inhibitors in advanced cutaneous squamous cell carcinoma: real-world data of a retrospective, multicenter study. Eur J Cancer. 2020;138:125–32.

    Article  CAS  Google Scholar 

  32. Hanna GJ, Ruiz ES, LeBoeuf NR, Thakuria M, Schmults CD, Decaprio JA, et al. Real-world outcomes treating patients with advanced cutaneous squamous cell carcinoma with immune checkpoint inhibitors (CPI). Br J Cancer. 2020;123:1535–42.

    Article  CAS  Google Scholar 

  33. In GK, Vaidya P, Filkins A, Hermel DJ, King KG, Ragab O, et al. PD-1 inhibition therapy for advanced cutaneous squamous cell carcinoma: a retrospective analysis from the University of Southern California. J Cancer Res Clin Oncol. 2021;147:1803–11.

    Article  CAS  Google Scholar 

  34. Hober C, Fredeau L, Pham-Ledard A, Boubaya M, Herms F, Celerier P, et al. Cemiplimab for locally advanced and metastatic cutaneous squamous-cell carcinomas: real-life experience from the French CAREPI Study Group. Cancers 2021;13:3547.

  35. Ben Ishai M, Tiosano A, Fenig E, Ben Simon G, Yassur I. Outcomes of vismodegib for periocular locally advanced basal cell carcinoma from an open-label trial. JAMA Ophthalmol. 2020;138:749–55.

    Article  Google Scholar 

  36. Eiger-Moscovich M, Reich E, Tauber G, Berliner O, Priel A, Ben Simon G, et al. Efficacy of vismodegib for the treatment of orbital and advanced periocular basal cell carcinoma. Am J Ophthalmol. 2019;207:62–70.

    Article  CAS  Google Scholar 

  37. Gershoni A, Tiosano A, Ben Ishai M, Barayev E, G JBS, Yassur I. Vismodegib improves quality of life in patients with periocular locally advanced basal cell carcinoma: subgroup analysis, STEVIE trial. Eye. 2022;36:407–13.

    Article  CAS  Google Scholar 

  38. Kahana A, Unsworth SP, Andrews CA, Chan MP, Bresler SC, Bichakjian CK, et al. Vismodegib for preservation of visual function in patients with advanced periocular basal cell carcinoma: The VISORB Trial. Oncologist. 2021;26:e1240–e1249.

    Article  CAS  Google Scholar 

  39. Wang DY, Salem JE, Cohen JV, Chandra S, Menzer C, Ye F, et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol. 2018;4:1721–8.

    Article  Google Scholar 

  40. Guillaume T, Puzenat E, Popescu D, Aubin F, Nardin C. Cemiplimab-rwlc in advanced cutaneous squamous cell carcinoma: real-world experience in a French dermatology department. Br J Dermatol. 2021;185:1056–8.

    Article  CAS  Google Scholar 

  41. Valentin J, Gerard E, Ferte T, Prey S, Dousset L, Dutriaux C, et al. Real-world safety outcomes using cemiplimab for cutaneous squamous cell carcinoma. J Geriatr Oncol. 2021;12:1110–3.

    Article  CAS  Google Scholar 

  42. Rischin D, Khushalani NI, Schmults CD, Guminski A, Chang ALS, Lewis KD, et al. Integrated analysis of a phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma: extended follow-up of outcomes and quality of life analysis. J Immunother Cancer. 2021;9:e002757.

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Author information

Author notes

  1. These authors contributed equally: Assaf Gershoni, Iftach Yassur.

Authors and Affiliations

  1. Ophthalmology Division, Rabin Medical Center—Beilinson Hospital, Petach Tikva, Israel

    Alon Tiosano, Meydan Ben-Ishai, Assaf Gershoni & Iftach Yassur

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Alon Tiosano, Meydan Ben-Ishai, Gal Markel, Noga Kurman, Assaf Gershoni & Iftach Yassur

  3. Ophthalmology Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel

    Yaacov Cnaany

  4. Davidoff Comprehensive Cancer Center, Rabin Medical Center—Beilinson Hospital, Petach Tikva, Israel

    Gal Markel & Noga Kurman

  5. Sharett Institute of Oncology, Hebrew University Hadassah Medical Center, Jerusalem, Israel

    Aron Popovtzer

  6. Oncology and Hematology Division, Emek Medical Center, Afula, Israel

    Gil Bar Sela

  7. Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Israel

    Guy Ben Simon

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Contributions

AG and AT acquired the data and drafted the manuscript. AT and MB-I analysed the data and aided in interpreting the results. YC, GM, NK, AP and GBS aided in data acquisition. GBS and IY designed the current study and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Iftach Yassur.

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Tiosano, A., Ben-Ishai, M., Cnaany, Y. et al. Primary cemiplimab treatment for orbital squamous cell carcinoma is effective and may alleviate the need for orbital exenteration. Eye (2023). https://doi.org/10.1038/s41433-022-02358-y

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