Combining Panitumumab With Anti-PD-1 Antibody in Cutaneous Squamous Cell Carcinoma of the Head and Neck After Inadequate Response to Anti-PD-1 Antibody Alone
August 2021 | Volume 20 | Issue 8 | Case Reports | 901 | Copyright © August 2021
Published online July 23, 2021
Emily Hsu MDa, Omar Eton MDb, Akshay V. Patel DOb, Richard Cartun PhDb, Jonathan S. Earle MDb, Laila O. Mnayer PhDb, Jennifer Kotowitz RN BSNb, Peter P. Yu MDb
aDepartment of Hematology and Oncology, University of Connecticut, Farmington, CT
bHartford Health Care Cancer Institute, Hartford, CT
Anti-epidermal growth factor receptor (EGFR) antibodies and anti-programmed cell death 1 protein (PD-1) antibodies have been used separately to treat metastatic cutaneous squamous cell carcinoma (cSCC). While two anti-EGFR antibodies have similar clinical activity, cetuximab is administered weekly, whereas panitumumab is administered every two weeks. This report details findings using panitumumab in combination with anti-PD-1 antibody in patients with relapsed refractory cSCC. Three consecutive patients with poor performance status and rapidly progressive recurrent cutaneous squamous cell carcinoma (cSCC) of the face or scalp signed informed consent to receive an anti-PD-1 antibody with the option to add panitumumab were there inadequate response. After 2, 5, and 7 cycles of anti-PD-1 antibody treatment, respectively, panitumumab was added and the combination was continued for 27, 7, and 5 cycles, respectively. Fatigue, rash, and hypomagnesemia were reported, consistent with expectations for either agent alone. All three patients achieved durable complete response. The favorable clinical outcomes support further evaluation of the combination of anti-PD1 and anti-EGFR antibodies to control refractory cSCC of the face or scalp. J Drugs Dermatol
. 2021;20(8):901-904. doi:10.36849/JDD.6175
The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing worldwide, with risk factors including cumulative exposure to ultraviolet light, photosensitizing agents, industrial carcinogens, smoking, immunosuppression, chronic wounds, inflammation, ionizing radiation, or rare inherited disorders. Most cSCC are curable with surgery alone.1
Locoregional or distant metastases occur in up to 5% of patients with cSCC. While cSCC, a malignancy of epidermal keratinocytes, often highly expresses the epidermal growth factor receptor (EGFR), EGFR mutation is uncommon.2 Primary cSCC of a sun-exposed area generally harbors a high tumor mutation burden (TMB) and often expresses programmed cell death ligand 1 (PD-L1) which can facilitate metastatic spread.3 These biomarkers and others such as the presence of tumor infiltrating lymphocytes (TIL) and the expression of interferon gamma are being evaluated to help guide treatment decisions.4 Monoclonal antibodies are often used to treat metastatic cSCC. FDA approved anti-programmed cell death 1 protein (anti-PD-1) antibodies include cemiplimab5 or pembrolizumab,6 other anti-PD-1 antibodies, like nivolumab,7 are also active. In small studies, anti-PD1 antibodies have response rates of 34 - 49% with responses lasting a median of 7–8 months. EGFR antibodies like cetuximab8 or panitumumab9 function as signal transduction inhibitors, while cetuximab also has anti-tumor immunogenic properties.10 Both anti-EGFR antibodies have similar response rates of 30 percent, lower than seen with anti-PD1 antibodies.11 It is to be determined whether these two treatment approaches can be safely combined for improved outcomes.
In one case report in 2018, cSCC of the auricle that was rapidly progressive despite surgery and radiation was successfully treated with the combination of cetuximab and nivolumab. The cetuximab was stopped early for cutaneous toxicity, while the nivolumab continued for a year, achieving a complete response (CR).12 It is indeterminate whether the tumor would have responded to nivolumab alone.