Cemiplimab as Immunotherapy for Locally Advanced Squamous Cell Carcinoma of the Eye
Authors: Jobanpreet Dhillon, Nishaant Bhambra, Daniel Q. Li, Sabrina Bergeron, Georges Shenouda, Miguel N. Burnier, Bryan P. Arthurs, Christian El-Hadad
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Title: Cemiplimab as Immunotherapy for Locally Advanced Squamous Cell Carcinoma of the Eye
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Purpose: Squamous cell carcinoma (SCC) is a highly prevalent malignant neoplasm of the eyelid and conjunctiva. While most cases of cutaneous SCC are amenable to curative surgery or radiotherapy, a small proportion of patients with locally advanced or metastatic SCC are limited to systemic therapy. Recently, programmed cell death protein-1 (PD-1) inhibitors have emerged as promising treatment for unresectable or metastatic SCC. Herein, we report two cases of primary SCC treated with the PD-1 inhibitor, cemiplimab. The first patient, presenting with T4aN1bM0 eyelid SCC treated with cemiplimab to complete resolution. The second patient, presenting with a T3N0M0 conjunctival SCC which was also treated with cemiplimab to achieve complete resolution.
Study Design: Case report and literature review.
Methods: Medical charts of patients were reviewed. Comprehensive literature review was conducted.
Case #1: The first patient was a 64-year-old male known for psoriasis and referred to the McGill University Health Centre (MUHC) by his dermatologist for a progressing left upper eyelid lesion. The lesion was previously biopsied by an outside ophthalmologist and reported as psoriasis. On exam, the patient exhibited a 4.5 x 3.0 cm pedunculated, inflamed mass of the left upper eyelid, advanced nuclear sclerotic cataract, and light perception vision. A repeat biopsy at the MUHC revealed invasive SCC. Additionally, biopsy of a suspicious lesion on patient’s left thigh revealed invasive SCC, thought to be a second primary given its significant epidermal connection on histopathological examination. Magnetic resonance imaging of the orbits revealed tumor invasion into the left lacrimal gland and extraconal fat without perineural spread. Whole-body PET-CT scan showed hypermetabolic lesions in left upper eyelid and ipsilateral cervical, parotid and periauricular nodes. A fine needle aspiration biopsy confirmed metastasis to the left parotid lymph node. Hence, the disease was staged as T4aN1bM0 as per the AJCC 8th edition for carcinoma of the eyelids. The patient was started on cemiplimab 350 mg IV q3 weeks. Following six cycles, a repeat PET-CT scan showed absence of hypermetabolic lesions in the left orbit and near-complete resolution of cutaneous lesion in left medial thigh. A left neck dissection confirmed absence of nodal metastasis post-therapy.
Case #2: The second patient was a 57-year-old female who first presented with a primary left conjunctival SCC with orbital extension, and following exenteration, presented with a second primary conjunctival SCC in the right eye 30 months later. The first conjunctival SCC demonstrated extension to the left lower lid margin and the globe of the left eye. Histopathological analysis showed an invasive neoplastic process, consistent with poorly differentiated carcinoma with areas of squamous and sebaceous differentiation. No lymphatic or metastatic spread was seen with carcinoma staging as T3N0M0. At the time, the only available treatment for extensive conjunctival carcinoma was orbital exenteration. Approximately 30 months later, the patient presented with as second primary SCC of the contralateral conjunctiva. At this point, cemiplimab was approved by Health Canada for treatment of metastatic or locally advanced cutaneous squamous cell carcinoma who are not candidates for surgery or radiotherapy. This patient received cemiplimab 350mg IV q3weeks. After nine cycles, the size of the lesion was greatly reduced. Histopathological analysis of the right conjunctiva showed no signs of malignancy, indicating complete resolution of the lesion.
Conclusions: The current cases provide support for the efficacy of cemiplimab as primary treatment for locally advanced or metastatic SSC of the conjunctiva and eyelid. Both patients remain under active surveillance through clinical appointments every 4-6 months to monitor for recurrence. Cemiplimab was approved by the USA’s Federal Drug Administration in September 2018, the same month the second patient presented with their first conjunctival carcinoma. If Health Canada had also approved cemiplimab at the same time, it is highly probable that the patient could have been binocular today. Nevertheless, immunotherapy offers a welcomed therapeutic advancement that merits consideration as first-line treatment in cases of locally invasive SCC.