Identifying candidates for immunotherapy with cemiplimab to treat advanced cutaneous squamous cell carcinoma: an expert opinion

Cutaneous squamous cell carcinoma (CSCC) is the second most common skin malignancy in white-skinned populations. Only a minority of patients (<5%) develop advanced disease, but this is often difficult to treat and characterised by a poor prognosis. Cemiplimab, a fully human IgG4 monoclonal antibody against programmed cell death-1 receptor, is indicated for advanced (i.e. locally advanced or metastatic) CSCC. Although the definition of metastatic CSCC is clear, there is currently no agreed definition of locally advanced CSCC. In recent guidelines, locally advanced CSCC was described as non-metastatic CSCC that is unlikely to be cured with surgery, radiotherapy or combination treatment. A multi-disciplinary advisory group of Italian CSCC experts was convened to develop criteria to assist in identifying appropriate candidates for cemiplimab therapy in advanced CSCC, based on the literature and clinical experience. In locally advanced CSCC, absolute, or mandatory, criteria for the use of cemiplimab are deep invasion, multiple lesions without defined margins, inadequate surgical excision margins and multiple recurrences, whereas relative criteria include large lesions, in critical or functionally significant areas and that are surgically complex. In addition, physicians should consider patient willingness/preferences (an absolute criterion), and their age and health status/comorbidities (relative criteria). It is hoped that these proposed absolute and relative criteria will help guide rational identification of patients who will receive maximum benefit from immunotherapy, while more clinical data accumulate.

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Immunotherapy for the Treatment of Cutaneous Squamous Cell Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.733917 ◽

2021 ◽

Vol 11 ◽

Author(s):

Andrea Boutros ◽

Federica Cecchi ◽

Enrica Teresa Tanda ◽

Elena Croce ◽

Riccardo Gili ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Standard Treatment ◽

Objective Response ◽

Locally Advanced ◽

Cutaneous Squamous Cell Carcinoma ◽

European Medicines Agency ◽

Definition Of

Cutaneous squamous cell carcinoma (CSCC) accounts for approximately 20% of all keratinocytic tumors. In most cases, the diagnosis and treatments are made on small, low-risk lesions. However, in about 5% of cases, CSCC may present as either locally advanced or metastatic (i.e. with locoregional lymph nodes metastases or distant localizations). Prior to the introduction of immunotherapy in clinical practice, the standard treatment of advanced CSCC was not clearly defined, and up to 60% of patients received no systemic therapy. Thanks to a strong pre-clinical rationale, clinical trials led to the FDA (Food and Drug Administration) and EMA (European Medicines Agency) registration of cemiplimab, a PD-1 inhibitor that achieved encouraging results in terms of objective response, overall survival, and quality of life. Subsequently, the anti-PD-1 pembrolizumab received the approval for the treatment of advanced CSCC by the FDA only. In this review, we will focus on the definition of advanced CSCC and on the current and future therapeutic options, with a particular regard for immunotherapy.

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Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 Study): an open-label, nonrandomized, multicenter, phase 2 trial

Annals of Oncology ◽

10.1016/j.annonc.2021.07.008 ◽

2021 ◽

Author(s):

B.G.M. Hughes ◽

E. Munoz-Couselo ◽

L. Mortier ◽

Å. Bratland ◽

R. Gutzmer ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Locally Advanced ◽

Cutaneous Squamous Cell Carcinoma ◽

Phase 2 ◽

Open Label ◽

Phase 2 Trial ◽

Multicenter Phase

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Cemiplimab in a very frail population of patients with advanced or metastatic cutaneous squamous cell carcinoma: A monocenter real-life experience from Italy.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21524 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21524-e21524

Author(s):

Michele Guida ◽

Annarita Fanizzi ◽

Davide Quaresmini ◽

Annalisa Nardone ◽

Andrea Armenio ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Antitumor Activity ◽

Cell Carcinoma ◽

Clinical Outcomes ◽

Squamous Cell ◽

Life Experience ◽

Locally Advanced ◽

Real Life ◽

Cutaneous Squamous Cell Carcinoma ◽

High Antitumor Activity

e21524 Background: Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer. Although representing less than 5% of all CSCCs, advanced stages are difficult to treat. Cemiplimab, an antiPD-1 monoclonal antibody, is the first approved immunotherapy in the US and EU for patients with locally advanced (laCSCC) or metastatic (mCSCC) CSCC. Phase I-II studies showed high antitumor activity and good tolerability, but few data are still available regarding cemiplimab in real life experience in non-selected patients. Methods: We recruited 30 consecutive patients with laCSCC (25 pts) and mCSCC (5 pts) treated with cemiplimab from August 2019 to November 2020 at our Institution. Median age was 81 years (range 36-95); 24 males; median ECOG PS 1 (range 0-2). Five patients had an immunosuppressive condition including 3 patients with stable hematologic malignancies and two patients on immunosuppressive therapy for kidney transplantation and Crohn’s disease, respectively. The majority of patients had comorbidities (median 3). Cemiplimab was administered at the flat dose of 350 mg i.v. every 21 days until disease progression or unacceptable toxicity. In all patients we evaluated clinical outcomes, toxicity, and associations between clinical outcomes and peripheral blood parameters. Results: We reported 23 responses (ORR 76.7%) with CR in 5 patients (16.7%). One patient had SD for 5 months. The global DCR was 80%. The median duration of response and PFS was not reached at a median follow-up of 6 months. We observed a higher ORR in head and neck primary tumours (87% vs. 42.9% of others, p = 0.016) and in patients with haemoglobin level > 12 g/dL (87.5% vs. 64.3%). No significative difference in ORR was observed with respect to the median age (81.3% in >81 years vs. 71.4% in < 81 years). Among the 5 patients with immunosuppressive status, a response was obtained in 4 patients (80%), including 1 CR. Nine patients died, 7 for PD and 2 for causes unrelated to the disease. Twenty patients (67.7%) still have an ongoing response. The treatment was well tolerated by the majority of patients. The most common adverse events were fatigue in 7 patients (23.3%) and skin toxicity in 10 patients (33.3%) including pruritus in 6 patients, rash in 3 patients, bullous erythema in 1 patient. Only 3 (10%) patients experienced severe (grade 3/4) toxicity. Three responder patients interrupted treatment (2 for toxicity after 7 and 9 cycles, and one for pre-existing dementia) but maintaining their response. Conclusions: In our real-life experience cemiplimab showed high antitumor activity with acceptable safety profile similar to those in selected patients of trials. Moreover, its antitumor activity resulted not impaired in very elderly patients or in those with immunocompromized status.

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