A, A patient with metastatic cutaneous squamous cell carcinoma (CSCC) with a nodule (arrowhead) in the carotid region before programmed cell death 1 (PD-1) inhibitor therapy. B, Complete resolution of neck mass (arrowheads) after PD-1 inhibitor therapy in the patient shown in A. C, A patient with CSCC of the left preauricular region with unclear primary location before PD-1 inhibitor therapy. D, Partial response with reduction in tumor size and ulceration after 10 months of pembrolizumab therapy in the patient shown in C.
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Tran DC, Colevas AD, Chang ALS. Follow-up on Programmed Cell Death 1 Inhibitor for Cutaneous Squamous Cell Carcinoma . JAMA Dermatol. 2017;153(1):92–94. doi:10.1001/jamadermatol.2016.3884
Cutaneous squamous cell carcinoma (CSCC) is one of the 2 most common types of human malignant tumors.1 Although most CSCCs are effectively treated with excision, recurrent disease near vital structures or metastasis can be challenging to treat. Currently, there is no accepted standard of care for unresectable or metastatic CSCCs, although platinum compounds, taxanes, and fluorouracil are commonly used. Recently, 2 reports of CSCC cases treated with programmed cell death 1 (PD-1) inhibitors have been published but contain limited follow-up times (<7 months).2,3 The safety profile of PD-1 inhibitors in CSCCs is also not well known. We present 6 consecutive cases of advanced CSCCs treated with PD-1 inhibitors, including an extended follow-up of 1 previously reported index case2 to 21 months of progression-free survival (PFS).
After approval from the Stanford Human Subjects Panel, 6 consecutive cases of unresectable and metastatic CSCCs treated with pembrolizumab (2 mg/kg every 3 weeks) or nivolumab (3 mg/m2 every 2 weeks) were selected from our clinical practice at the Stanford University Medical Center from October 1, 2014, through May 1, 2016. The main outcomes of interest were clinical response, durations of PFS, and type and severity of adverse events. The data were deidentified. Patients whose images are shown in the figures have provided written consent for publication.
The index case,2 previously published after 5 months of follow-up, is now reported after 21 months of PFS. Briefly, the patient is a white man in his 70s with a right temple CSCC with perineural invasion and subsequent recurrence necessitating multiple operations (including parotidectomy, lymph node dissections, and cranial nerve VII sacrifice with orbital exenteration), radiotherapy, and cetuximab treatment (Table and Figure). The tumor was subsequently deemed unresectable because residual disease was discovered, extending up to the skull base adjacent to the basilar vascular system. The patient started pembrolizumab monotherapy with ongoing partial response at 21 months. His therapy was complicated by severe weakness attributable to hypocortisolism and hypothyroidism, which resolved with institution of systemic corticosteroids and thyroid hormone therapy. His additional adverse effects included mild arthralgia and mild weight loss.
Additional cases are presented in the Table and Figure, including case 2, which involved a patient with a complete response. Of the 6 cases presented, the median age of the patients at CSCC diagnosis was 72.6 years (range, 60-82 years). All patients were immunocompetent.
Five of 6 patients (83%) experienced a clinical response, with 1 complete and 4 partial responses. One patient (17%) had progressive disease. The median duration of PD-1 inhibitor exposure was 8 months (range, 3-21 months), and the longest PFS was 21 months. Two of 6 patients experienced severe adverse events, namely, fatigue caused by endocrine hypofunction and hip fracture, both of which were treated and resolved. The most common adverse effect was mild fatigue, seen in 5 patients (83%). None of the other adverse effects occurred in more than 1 patient.
Current conventional chemotherapy treatment options for unresectable and metastatic cutaneous CSCCs remain limited. For instance, the largest retrospective study to date of 25 patients with high-risk CSCCs reported response rates of only 50% for locally advanced and 17% for metastatic CSCCs. The median PFS was only 5.5 months.4 Although our data are from a case series and not a prospective clinical trial, they represent all the patients treated in our clinical practice with PD-1 inhibitors to date, with response rates and PFS exceeding the previous report.4 Our report adds useful data to support the use of anti–PD-1 inhibitors for unresectable CSCCs, a finding that needs confirmation through larger clinical trials.
In addition, all cases included in our series were in immunocompetent individuals. Because immunosuppressed individuals, including patients undergoing solid organ transplant, have an extremely high rate of CSCCs5 and do poorly when treated with conventional chemotherapy, future studies are needed to determine whether PD-1 inhibitors may be beneficial for this population.
Corresponding Author: Anne Lynn S. Chang. MD, Department of Dermatology, Stanford University School of Medicine, 450 Broadway St, Mail Code 5334, Pavilion C, Second Floor, Redwood City, CA 94063 (firstname.lastname@example.org).
Accepted for Publication: August 22, 2016.
Published Online: October 26, 2016. doi:10.1001/jamadermatol.2016.3884
Author Contributions: Drs Colevas and Chang had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Tran, Colevas.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Tran, Chang.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Tran.
Administrative, technical, or material support: All authors.
Study supervision: Chang.
Conflict of Interest Disclosures: Dr Chang reported serving as a clinical investigator for studies sponsored by Merck, the maker of pembrolizumab, and for studies sponsored by Genentech and Novartis. No other disclosures were reported.
Additional Contributions: Richard Luciano, NP, Stanford Hospital and Clinics, assisted with data acquisition on 1 case. We thank the patients for granting permission to publish this information.