Cetuximab-based management of metastatic cutaneous squamous cell carcinoma in a heart transplant recipient: A case report and literature review

 Corresponding author: Serge Emmanuel Bambule Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution License 4.0. Cetuximab-based management of metastatic cutaneous squamous cell carcinoma in a heart transplant recipient: A case report and literature review Serge Emmanuel Bambule 1, 2. *, Francia Holguin 3, Hubert Pheulpin 3, Pierre Zuech 3, Larisa Martanovschi 3, Gabriela Tossen 3 and Geraldine Salmeron 3 1 Medical Oncology department, Faculty of Medicine and Pharmacy of Casablanca, Morocco. 2 Internal Medicine department, Faculty of Medicine, University of Kinshasa, DRC. 3 Hematology and Medical Oncology department, Poissy Intercommunal Hospital Center, France. World Journal of Advanced Research and Reviews, 2025, 27(02), 812-817 Publication history: Received on 06 July 2025; revised on 09 August; accepted on 12 August 2025 Article DOI: https://doi.org/10.30574/wjarr.2025.27.2.2931 Abstract Background: Solid organ transplant recipients face a higher risk of cutaneous squamous cell carcinoma (cSCC) due to long-term immunosuppression. Managing metastatic cSCC in these patients is challenging because immune checkpoint inhibitors (ICIs) may cause graft rejection. Case Presentation: A 67-year-old male heart transplant recipient developed multiple cSCCs with lung metastases during his illness. After surgery and radiotherapy, disease progression prompted systemic therapy with carboplatin and cetuximab. The patient achieved a complete metabolic response after seven cycles, with no graft rejection or severe side effects. Cetuximab maintenance therapy sustained the response. Conclusion: Cetuximab offers a safe and effective treatment for advanced cSCC in heart transplant recipients, avoiding the risks of ICIs. This case shows that Cetuximab can be a good alternative treatment. Keywords: Cutaneous squamous cell carcinoma; Heart transplantation; Immunosuppression; Cetuximab 1. Introduction Heart transplantation improves survival in patients with end-stage heart disease, but long-term immunosuppression increases the risk of cancers, especially cutaneous squamous cell carcinoma (cSCC). cSCC accounts for approximately 10% of cases in heart transplant recipients and is often more aggressive, with a higher chance of metastasis compared to the general population [1]. These tumors commonly occur on the head and neck[2] . Immune checkpoint inhibitors (ICIs), are effective in non-transplant patients, are risky for transplant recipients due to potential graft rejection[3–5]. Cetuximab, an anti-EGFR monoclonal antibody, is a promising alternative, but its use in heart transplant patients is not well studied. This case report describes a heart transplant recipient with metastatic cSCC successfully treated with cetuximab, demonstrating a tailored treatment approach. 2. Case presentation A 67-year-old male, with no history of smoking, alcohol use, or family cancer, underwent heart transplantation in 2021 for end-stage ischemic cardiomyopathy. He was maintained on tacrolimus (6 mg/day, mycophenolate mofetil (500 mg/day), and prednisone (5 mg/day). In May 2022, actinic keratoses on his forehead and vertex were treated with photodynamic therapy and cryotherapy, with regular dermatological follow-up. World Journal of Advanced Research and Reviews, 2025, 27(02), 812-817 813 In October 2022, three exophytic, ulcerative lesions appeared on the left forehead, left vertex, and right wrist. (Figure 1) Figure 1 Ulcerative, and exophytic skin lesion located on the dorsal aspect of the right wrist Biopsies confirmed well-differentiated cSCC, staged per the 8th AJCC edition: • Right wrist: pT2 R0, no vascular emboli or perineural invasion • Left vertex: pT2 R1 (deep margin), perineural invasion present. • Left forehead: pT1 R0, vascular emboli and perineural invasion presents. In January 2023, surgical excision and local flap reconstruction were performed. Intraoperative fine needle aspiration of a left cervical lymph node showed metastatic cSCC. A PET-CT in March 2023 revealed hypermetabolic left cervical lymphadenopathy (level Va) and a postsurgical inflammatory frontal focus. Re-excision of the vertex lesion and lymph node dissection (15 nodes) confirmed metastatic spread with capsular rupture. Adjuvant cervical radiotherapy (69.96 Gy in 33 fractions) was given from May to June 2023. In January 2024, PET-CT detected three bilateral pleuropulmonary nodules (12 mm right upper lobe, 10 mm left upper lobe, 19 mm right lower lobe) (figure 2 and figure 3), treated with stereotactic radiotherapy in March 2024. Figure 2 Hypermetabolic pulmonary nodule of 19 mm in right lower lobe World Journal of Advanced Research and Reviews, 2025, 27(02), 812-817 814 Figure 3 Hypermetabolic pulmonary nodule nodule of 12 mm in right upper lobe In October 2024, a new 15 mm left lower lobe nodule and right basal condensation (SUVmax 2.9) appeared. (Figure 4) Figure 4 hypermetabolic pulmonary nodule (left) and Pulmonary condensation in the apical segment of the right lower lobe (Right) After multidisciplinary discussion, systemic therapy began with carboplatin (AUC5) and cetuximab (400 mg/m² loading dose, then 250 mg/m² weekly), alongside reduced immunosuppression (tacrolimus 4 mg/day). After seven cycles, a March 2025 PET-CT showed a complete morpho-metabolic response. Cetuximab maintenance (500 mg every two weeks) sustained the response, confirmed by a June 2025 PET-CT. Side effects included grade II acneiform rash, xerosis with digital fissures, and grade I hypomagnesemia, managed with doxycycline, emollient and healing creams, and oral magnesium supplementation. No graft rejection or cardiovascular toxicity occurred, and the patient continues cetuximab maintenance. 3. Discussion Managing metastatic cSCC in heart transplant recipients is complex, requiring both cancer control and graft protection. cSCC is a common cancer after a heart transplant (10% of cases), often head and neck-based (70%) and more metastatic than in no transplant patients[1,2]. Immunosuppression with tacrolimus, mycophenolate mofetil, and prednisone prevents graft rejection but promotes tumor growth by inhibiting T-cell activation[6]. In this case, immunosuppression likely drove cSCC development, as the patient had no significant UV chronic exposure. Tacrolimus may increase skin cancer risk compared to sirolimus, which could offer protective effects[1], raising important considerations for long-term immunosuppressive strategies. ICIs like cemiplimab are effective for advanced cSCC in the general population, with 47–50% response rates[7,8],but they carry a 41% graft rejection risk in transplant patients, including 20% in heart transplant cases[9]. World Journal of Advanced Research and Reviews, 2025, 27(02), 812-817 815 PD-1 inhibitors (nivolumab, pembrolizumab) carry higher rejection risks than CTLA-4 inhibitors like ipilimumab, though the latter is less effective for cSCC [9]. Immunosuppressants may also attenuate ICI efficacy [3–5]. Other therapies such as bispecific antibodies or CAR-T cells, also risk rejection [10,11]. Cetuximab, targeting EGFR, overexpressed in 80–100% of cSCCs ,inhibits tumor growth and angiogenesis without compromising graft integrity [12]. In this case, carboplatin-cetuximab achieved a complete response, sustained with cetuximab maintenance. Literature supports these findings: a study of 10 cSCC patients ineligible for immunotherapy reported an 80% disease control rate with cetuximab, including 10% complete responses[13]. Two phase II trials showed 78% and 69% disease control rates with cetuximab, respectively, with better outcomes when combined with carboplatin [14,15]. Side effects were manageable, following guidelines [16]. The table below summarizes cetuximab tolerance in transplant recipients with various cancers and immunosuppressive regimens. Table 1 Cetuximab Tolerance in Transplant Recipients cancer Type Transplant Immunosuppression Cancer treatment Adverse Events Mydin et al. [18] Piriform sinus SCC Liver Mycophenolate, tacrolimus Cetuximab + radiotherapy Acneiform rash and grade III dysphagia JA, et al. [19] Metastatic cSCC Lung Sirolimus Cetuximab monotherapy Grade 5 Toxicity Holguin et al .[20] Case I : Laryngeal SCC Liver Tacrolimus, mycophenolate, everolimus Paclitaxel + Cetuximab Grade III neutropenia Case II : Laryngeal SCC Liver Tacrolimus Cetuximab + radiotherapy GGT and PAL elevation , Acneiform rash and hypomagnesemia Kalapurakal SJ et al. [21] cSCC, Basal cell carcinoma Kidney Mycophenolate Cetuximab monotherapy No grade 3 and 4 toxicities Julian A. MarinAcevedo et al [13] Advanced or metastatic cSCC Kidney Cyclosporine, prednisone Tacrolimus Tacrolimus, mycophenolate Cetuximab monotherapy Acneiform Rash (grade 1–2), Hypomagnesemia (grade 1–2) Liver Tacrolimus, mycophenolate Cetuximab + radiotherapy Hypomagnesemia, Acneiform rash (grade 1–2) Heart Tacrolimus, prednisone Cetuximab + radiotherapy Grade 5 toxicity Immunosuppression was adjusted (tacrolimus reduced to 4 mg/day, mycophenolate discontinued), with close cardiology and oncology collaboration ensuring treatment success. The sustained complete response indicates substantial efficacy of Cetuximab-based regimens in solid organ transplant recipients with advanced cSCC [17]. World Journal of Advanced Research and Reviews, 2025, 27(02), 812-817 816 4. Conclusion cSCC is a common and serious complication in heart transplant recipients, affecting up to 10% due to immunosuppression. Cetuximab is a safe and efficacious treatment option, avoiding the graft rejection risks of ICIs. This study and the supporting literature suggest that cetuximab could be a treatment of choice for advanced CSC in transplant patients, provided it is followed appropriately. Compliance with ethical standards Disclosure of conflict of interest No conflict of interest to be disclosed. Statement of ethical approval The present research work does not contain any studies performed on animals/humans subjects by any of the authors. Statement of informed consent Informed consent was obtained from all individual participants included in the study. References [1] Yang Y, Song Y, Liu F, Yao H. Incidence and risk factors for skin cancer after heart transplantation: a systematic review and meta-analysis. Arch Dermatol Res. 2025; 317:248. [2] Campos GR, Boin I de FSF, de Campos Junior ID, Cintra ML. Study of factors affecting the incidence of skin cancer in patients after liver transplant. An Bras Dermatol. 2017; 92:492‑8. [3] Pluchart H, Ferrer L, Giovannini D, Tetaz R, Pinsolle J, Stephanov O, et al. Utilisation concomitante du nivolumab et d’immunosuppresseurs chez un patient greffé rénal. Revue des Maladies Respiratoires. 2019;36:1064‑8. [4] d’Izarny-Gargas T, Durrbach A, Zaidan M. Efficacy and tolerance of immune checkpoint inhibitors in transplant patients with cancer: A systematic review. American Journal of Transplantation. 2020;20:2457‑65. [5] Herbst RS, Baas P, Kim D-W, Felip E, Pérez-Gracia JL, Han J-Y, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. The Lancet. 2016; 387:1540‑50. [6] Boyd K, Shea SM, Patterson J. Cetuximab for treatment of advanced squamous cell carcinoma in solid organ transplant recipients. Wien Med Wochenschr. 2013; 163:372‑5. [7] 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. [8] Research C for DE and. FDA approves cemiplimab-rwlc for metastatic or locally advanced cutaneous squamous cell carcinoma. FDA [Internet]. 2019 [cité 23 juin 2025]; Disponible sur: https://www.fda.gov/drugs/drugapprovals-and-databases/fda-approves-cemiplimab-rwlc-metastatic-or-locally-advanced-cutaneoussquamous-cell-carcinoma [9] Kumar V, Shinagare AB, Rennke HG, Ghai S, Lorch JH, Ott PA, et al. The Safety and Efficacy of Checkpoint Inhibitors in Transplant Recipients: A Case Series and Systematic Review of Literature. Oncologist. 2020; 25:505‑14. [10] Moon D, Tae N, Park Y, Lee S-W, Kim DH. Development of Bispecific Antibody for Cancer Immunotherapy: Focus on T Cell Engaging Antibody. Immune Netw. 2022; 22:e4. [11] https://experts-recherche-lymphome.org/wp-content/uploads/2024/05/la-saga-des-car-t-le-monde-2-mai2024.pdf [Internet]. [cité 23 juin 2025]. Disponible sur: https://experts-recherche-lymphome.org/wpcontent/uploads/2024/05/la-saga-des-car-t-le-monde-2-mai-2024.pdf [12] Maubec E, Duvillard P, Velasco V, Crickx B, Avril M-F. Immunohistochemical analysis of EGFR and HER-2 in patients with metastatic squamous cell carcinoma of the skin. Anticancer Res. 2005; 25:1205‑10. [13] Marin-Acevedo JA, Withycombe BM, Kim Y, Brohl AS, Eroglu Z, Markowitz J, et al. Cetuximab for ImmunotherapyRefractory/Ineligible Cutaneous Squamous Cell Carcinoma. Cancers (Basel). 2023; 15:3180. World Journal of Advanced Research and Reviews, 2025, 27(02), 812-817 817 [14] Preneau S, Rio E, Brocard A, Peuvrel L, Nguyen J-M, Quéreux G, et al. Efficacy of cetuximab in the treatment of squamous cell carcinoma. J Dermatolog Treat. 2014; 25:424‑7. [15] Schenk KM, Deutsch JS, Chandra S, Davar D, Eroglu Z, Khushalani NI, et al. Nivolumab + Tacrolimus + Prednisone ± Ipilimumab for Kidney Transplant Recipients With Advanced Cutaneous Cancers. JCO. 2024;42:1011‑20. [16] Visseaux DNJ Dr Laetitia. Principales toxicités cutanées associées aux inhibiteurs de l’EGFR [Internet]. Onko+. 2024 [cité 7 janv 2025]. Disponible sur: https://onko.fr/principales-toxicites-cutanees-associees-auxinhibiteurs-de-legfr/ [17] Kim C, Cheng J, Colegio OR. Cutaneous squamous cell carcinomas in solid organ transplant recipients: emerging strategies for surveillance, staging, and treatment. Seminars in Oncology. 2016; 43:390‑4. [18] Mydin AR, Armstrong JG. Radiotherapy Plus Cetuximab is Safe in a Head and Neck Cancer Patient on Immunosuppressants for Liver Transplant. Clinical Oncology. 2007; 19:365‑6. [19] Leard LE, Cho BK, Jones KD, Hays SR, Tope WD, Golden JA, et al. Fatal Diffuse Alveolar Damage in Two Lung Transplant Patients Treated With Cetuximab. The Journal of Heart and Lung Transplantation. 2007;26:1340‑4. [20] Holguin F, Rubió-Casadevall J, Saigi M, Marruecos J, Taberna M, Tobed M, et al. Cetuximab as treatment for head and neck cancer patients with a previous liver transplant: report of two cases. Journal of Chemotherapy. 2017;29:310‑3. [21] Kalapurakal SJ, Malone J, Robbins KT, Buescher L, Godwin J, Rao K. Cetuximab in Refractory Skin Cancer Treatment. J Cancer. 2012;3:257‑61.