Abstract
Non-melanoma skin cancers are one of the most common cancers diagnosed worldwide, with the highest incidence in Australia and New Zealand. Systemic treatment of locally advanced and metastatic cutaneous squamous cell carcinomas has been revolutionized by immune checkpoint inhibition with PD-1 blockade. We highlight treatment issues distinct to the management of the disease including expansion of the traditional concept of pseudoprogression and describe delayed responses after immune-specific response criteria confirmed progressive disease with and without clinical deterioration. We term this phenomenon “delayed response after confirmed progression (DR)”. We also discuss the common development of second primary tumors, heterogeneous disease responses, and expanding clinical boundaries for immunotherapy use.
Highlights
Non-melanoma skin cancers (NMSC) predominantly basal cell carcinomas (BCC) and cutaneous squamous cell carcinomas (CSCC) are the most frequently diagnosed cancer in North America and Australia/New Zealand [1]
The morbidity related to disease is significant and accounts for the most common cancer-related cause for hospitalization in Australia exacerbated by the multiplicity of skin cancer excisions [2,3,4]
The KEYNOTE-629 study showed that pembrolizumab is efficacious (ORR 34%; 95% CI: 25- 44) [10], which led to Food and Drug Administration (FDA) approval
Summary
Non-melanoma skin cancers (NMSC) predominantly basal cell carcinomas (BCC) and cutaneous squamous cell carcinomas (CSCC) are the most frequently diagnosed cancer in North America and Australia/New Zealand [1]. Our observation of DR and scenarios discussed further below, caution against a nihilistic approach to CSCC patient management when using immunotherapy These cases highlight the important consideration of the timing and method of disease response assessments and the limitations of most criteria to capture pseudoprogression/DR, response rates and best overall response (BOR) assessments as part of clinical trial reporting. Ongoing immunotherapy secured a complete clinical response for the left elbow lesion by Day 141 with imaging showing no identifiable tumor (nominal RECIST measurement of 5mm). Few treatment contraindications exist and few comorbidities raise concern including extreme age, dialysis, other synchronous malignancies requiring treatment, and poor ECOG performance status This is a paradigm change in our approach to patients with CSCC and is paramount given the dramatic response rates achieved by therapy, providing symptomatic and durable control. Comprehensive profiling of immunotherapy exposed tumors, including single cell sequencing approaches, will be important to further clarify inter-tumoral, intra-tumoral and tumor microenvironment molecular processes that underpin the described clinical concepts [48, 49]
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