What are the immunotherapy treatment options for Squamous Cell Carcinoma (SCC)?

From the Guidelines

Immunotherapy treatment options for Squamous Cell Carcinoma (SCC) include combination therapy with platinum-based doublet chemotherapy and immunotherapy, such as pembrolizumab or cemiplimab-rwlc, as well as dual immunotherapy with nivolumab and ipilimumab.

Key Treatment Options

• Pembrolizumab plus chemotherapy: The 5-year update of the phase III KEYNOTE-407 trial reported a 5-year OS rate of 18.4% versus 9.7% in favor of pembrolizumab plus chemotherapy (HR, 0.71 [95% CI, 0.59 to 0.85]) 1.
• Cemiplimab-rwlc plus chemotherapy: The EMPOWER-Lung 329 trial showed improvement in benefit over chemotherapy alone in patients with squamous cell carcinoma histology, with a median OS of 22.3 months (95% CI, 15.7 to 27.2) versus 13.8 months (95% CI, 9.3 to 18.0) with chemotherapy alone (HR, 0.61 [95% CI, 0.42 to 0.87]) 1.
• Nivolumab and ipilimumab dual immunotherapy: The 4-year follow-up results from the Checkmate 9LA trial showed long-term survival benefits with nivolumab along with ipilimumab with two cycles of chemotherapy compared to four cycles of chemotherapy alone in chemotherapy-naïve patients with metastatic NSCLC, including squamous type (HR, 0.74 [95% CI, 0.63 to 0.87]) 1.

Patient Selection

• PD-L1 expression: Patients with PD-L1 TPS >50% may benefit from monotherapy immunotherapy, while those with PD-L1 TPS 1%-49% may benefit from combination therapy with chemotherapy and immunotherapy 1.
• Performance status: Patients with PS 0-2 may be eligible for immunotherapy, although guidelines recommend a patient-centered approach to ensure the most appropriate treatment based on clinicopathologic characteristics, treatment history, and personal goals for treatment 1.

Additional Considerations

• Biomarker-driven approach: Investigation of additional predictive biomarkers, such as PD-L1 expression, may facilitate selection of patients who are most likely to benefit from immunotherapy 1.
• Second-line treatment: Immunotherapy with nivolumab, pembrolizumab, or atezolizumab may be considered as second-line treatment for patients with advanced SqCLC who have progressed after first-line chemotherapy 1.

From the Research

Immunotherapy Treatment Options for Squamous Cell Carcinoma (SCC)

• Immunotherapy has emerged as a promising new treatment modality for head and neck cancer, offering the potential for targeted and effective cancer management 2.
• Important contributions are made by immunotherapies, including adaptive cell therapy (ACT) and immune checkpoint inhibitor therapy, in the management of head and neck squamous cell carcinoma (HNSCC) 2.
• Immune checkpoint inhibitors target proteins such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to enhance the immune response against cancer cells 2, 3.
• The CTLA-4 inhibitors, such as ipilimumab and tremelimumab, have been approved for early-stage clinical trials and have shown promising outcomes in terms of tumor regression and durable responses in patients with advanced HNSCC 2.
• Checkpoint inhibitors, such as cemiplimab and pembrolizumab, have achieved high response rates and survival with fewer toxicities than other available systemic agents for cutaneous squamous cell carcinomas (cSCCs) 4.
• Pembrolizumab and nivolumab are anti-PD-1 immune checkpoint inhibitors that have been approved by the US Food and Drug Administration (FDA) for the treatment of patients with recurrent squamous cell carcinoma of the head and neck (HNSCC) that is refractory to platinum-based regimens 5.

Types of Immunotherapy

• Immune checkpoint inhibitors: target proteins such as PD-1 and CTLA-4 to enhance the immune response against cancer cells 2, 3.
• Adaptive cell therapy (ACT): a type of immunotherapy that involves the use of immune cells, such as T cells, to recognize and eliminate cancer cells 2.
• Costimulatory agonists: a type of immunotherapy that aims to enhance the activation of immune cells, such as T cells, to recognize and eliminate cancer cells 6.
• Antigenic vaccines: a type of immunotherapy that aims to stimulate the immune system to recognize and eliminate cancer cells by targeting specific antigens 6.
• Oncolytic virus therapy: a type of immunotherapy that uses viruses to selectively infect and kill cancer cells, while also stimulating an immune response against the cancer 6.

Combination Therapies

• Combination therapies using anti-CTLA-4 inhibitors, tyrosine kinase inhibitors, and immune accelerators are currently under investigation for the treatment of squamous cell carcinoma of the head and neck 3.
• Combination strategies of systemic therapy and surgery or radiotherapy are being investigated for the treatment of cutaneous squamous cell carcinomas (cSCCs) 4.