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“About 95 percent of squamous cell carcinomas (SCCs) of the skin are detected early, when they are easiest to treat and cure. The remaining 5 percent of SCC cases have advanced to such an extent that they are far more dangerous and challenging to treat…
The disease is also known as advanced cutaneous squamous cell carcinoma (cSCC). Adding the word “cutaneous” identifies it as a skin cancer and differentiates it from squamous cell carcinomas that can arise in other areas inside the body such as the mucous membranes in the mouth, throat, lungs or genital regions…
When a squamous cell carcinoma of the skin has spread extensively or aggressively, or has resisted multiple treatments and repeatedly recurred, it is considered to be advanced.
These tumors include:
“Non-melanoma skin cancers are the most prevalent form of cancer, with cutaneous squamous cell carcinoma (cscc) being the 2nd most common type. Patients presenting with high-risk lesions associated with locally advanced or metastatic cscc face high rates of recurrence and mortality. Accurate staging and risk stratification for patients can be challenging because no system is universally accepted, and no Canadian guidelines currently exist.
Patients with advanced cscc are often deemed ineligible for either or both of curative surgery and radiation therapy (rt) and, until recently, were limited to off-label systemic cisplatin–fluorouracil or cetuximab therapy, which offers modest clinical benefits and potentially severe toxicity.
A new systemic therapy, cemiplimab, has been approved for the treatment of locally advanced and metastatic cscc. In the present review, we provide recommendations for patient classification and staging based on current guidelines, direction for determining patient eligibility for surgery and rt, and an overview of the available systemic treatment options for advanced cscc and of the benefits of a multidisciplinary approach to patient management…
Patients with high-risk locally advanced or metastatic cscc face poor outcomes and few treatment options. Accurate staging of these patients is challenging given the inconsistent definitions of the features that constitute high-risk disease and the techniques to apply.
For patients with advanced cscc deemed ineligible for either or both of curative surgery or rt, treatment options were, until recently, limited to systemic cisplatin–5fu chemotherapy or off-label use of the egfr inhibitor cetuximab.
Unfortunately, the clinical benefits of those therapies in cscc are modest, and adverse events are frequent and potentially severe. The immune checkpoint inhibitor cemiplimab, which recently obtained Health Canada and U.S. Food and Drug Administration approval, is the first approved therapy indicated for the treatment of advanced cscc, and evidence is emerging to suggest that it could be promising, given its tolerability and efficacy. After the recent approval of cemiplimab, future studies should explore the potential uses of this new agent in an adjuvant setting and also the best therapeutic options for patients who relapse after anti–PD-1 immunotherapy. Continued research is also needed to provide better disease management options for immunosuppressed patients.
Regardless of the treatment selected, patient care should take a multidisciplinary approach. Multidisciplinary tumour boards should be considered when the path of treatment is unclear or in complex and high-risk cases. To further facilitate the quality of patient care and to increase accessibility, individual centres should consider the development of regional multidisciplinary teams, and tumour boards can leverage technology for wider reach.
“A fully human anti–programmed death 1 (PD-1) monoclonal antibody is safe and effective for patients with unresectable, locally advanced, or metastatic cutaneous squamous cell carcinoma (CSCC)…
There is no widely accepted standard of care for unresectable, locally advanced, or metastatic CSCC. Conventional chemotherapy can induce tumor response, but often is poorly tolerated among older patients with CSCC…
The most common treatment-related adverse event of any grade was fatigue (19.2%). One grade 3 or higher event was noted for AST elevation, ALT elevation, arthralgia, and rash. Two patients discontinued treatment due to treatment-related adverse events. Two patients died within 30 days of the last dose, but this was considered unrelated to the drug.
“This is the first prospective study of a PD-1 inhibitor in patients with advanced CSCC. REGN2810 was generally well tolerated in this predominantly older population,” concluded Papadopoulos.
Both locally advanced and metastatic CSCC are highly responsive to the drug, “and durability is emerging,” he said. “A unifying characteristic of cutaneous malignancies appears to be responsiveness to immune checkpoint inhibition.”