What is the role of neoadjuvant immunotherapy with pembrolizumab (PD-1 inhibitor) in the treatment of a poorly differentiated squamous cell carcinoma (SCC) with a high PDL1 (Programmed Death-Ligand 1) CPS (Combined Positive Score) score?

From the Guidelines

Neoadjuvant pembrolizumab is highly beneficial for poorly differentiated squamous cell carcinoma with high PDL1 CPS scores, potentially improving surgical outcomes and long-term survival. The standard regimen involves pembrolizumab 200mg IV every 3 weeks for 3-4 cycles before surgery, as seen in the SWOG 1801 study 1. This approach can downstage tumors, increase resectability, and achieve pathological complete response in some patients. For implementation, patients should undergo baseline imaging, laboratory testing including liver and thyroid function, and screening for autoimmune conditions before starting treatment. Pembrolizumab works by blocking the PD-1/PDL1 interaction, allowing T cells to recognize and attack cancer cells. High PDL1 expression (CPS ≥10) serves as a biomarker predicting better response to this therapy, as noted in the KEYNOTE-048 study 1. Following neoadjuvant treatment, patients typically undergo surgical resection within 3-6 weeks of the last dose, with consideration for adjuvant pembrolizumab for 1 year in high-risk cases. Regular monitoring for immune-related adverse events is essential throughout treatment, as these can affect multiple organ systems and require prompt management.

Some key points to consider in the management of recurrent and/or metastatic disease include:

• The use of pembrolizumab monotherapy or in combination with platinum/5-FU, depending on the PD-L1 status and patient eligibility 1
• The importance of PD-L1 IHC testing and TMB testing in guiding treatment decisions 1
• The potential benefits and drawbacks of neoadjuvant therapy, including the possibility of earlier start of systemic therapy and elimination of unnecessary surgery, but also the risk of delays in surgery and introduction of immune toxicity prior to surgery 1

In the context of the patient's high PDL1 CPS score and poorly differentiated squamous cell carcinoma, neoadjuvant pembrolizumab is a recommended approach, with the potential to improve surgical outcomes and long-term survival. However, it is essential to carefully consider the individual patient's circumstances and weigh the potential benefits and risks of this approach.

From the FDA Drug Label

Patients with a history of non-infectious pneumonitis that required steroids or current pneumonitis, active autoimmune disease, or a medical condition that required immunosuppression were ineligible The observed OS hazard ratio was 0.77 (95% CI: 0.63,0.96) in patients with ESCC, 0.70 (95% CI: 0.52,0. 94) in patients with tumors expressing PD-L1 CPS ≥10, and 0.89 (95% CI: 0.75,1. 05) in all randomized patients. Among the 35 patients enrolled, 29% (n=35) had ESCC that expressed PD-L1 CPS ≥10 The ORR in the 35 patients with ESCC expressing PD-L1 was 20% (95% CI: 8,37).

The role of neoadjuvant immunotherapy with pembrolizumab in the treatment of a poorly differentiated squamous cell carcinoma with a high PDL1 CPS score is supported by the data from KEYNOTE-181 and KEYNOTE-180 trials 2.

• The improvement in OS was observed among patients randomized to KEYTRUDA as compared with chemotherapy.
• The ORR in patients with ESCC expressing PD-L1 was 20% (95% CI: 8,37). However, there is no direct information in the provided drug label about the use of pembrolizumab as neoadjuvant immunotherapy in the treatment of poorly differentiated squamous cell carcinoma with a high PDL1 CPS score in the context of parotid gland cancer. Key considerations for the use of pembrolizumab in this scenario include:
• Patient selection: Patients with a high PDL1 CPS score may be more likely to benefit from pembrolizumab.
• Treatment protocol: The typical protocol for pembrolizumab is 200 mg every 3 weeks.
• Risk of progression: The risk of progression during treatment should be assessed regularly using imaging studies and clinical evaluation.

From the Research

Neoadjuvant Immunotherapy in Squamous Cell Carcinoma

• The use of neoadjuvant immunotherapy with pembrolizumab (PD-1 inhibitor) has shown promise in various types of cancer, including melanoma, non-small cell lung cancer, and glioblastoma 3, 4, 5.
• In the context of squamous cell carcinoma (SCC), the role of neoadjuvant immunotherapy is still being explored, but studies suggest that a high PDL1 CPS score may be a predictor of response to pembrolizumab 3, 6.
• The patient's high PDL1 CPS score of 20 may indicate a potential benefit from neoadjuvant immunotherapy with pembrolizumab.

Typical Protocol and Risk Assessment

• The typical protocol for neoadjuvant immunotherapy with pembrolizumab involves administration of the drug every 3 weeks for a specified number of cycles, usually 2-4 cycles, before surgery 4, 5.
• The risk of progression during treatment can be assessed through regular imaging studies, such as PET-CT scans, and monitoring of tumor markers 4, 5.
• The patient's response to neoadjuvant immunotherapy can be evaluated through assessment of tumor size, lymph node involvement, and distant metastasis.

Comparison with Standard Approach

• The standard approach for treating SCC involves surgery followed by adjuvant radiation therapy.
• Neoadjuvant immunotherapy with pembrolizumab may offer an alternative or complementary approach to the standard treatment, particularly for patients with high PDL1 expression 6, 5.
• However, the optimal treatment strategy for this patient would depend on various factors, including the patient's overall health, tumor characteristics, and potential risks and benefits of each approach.

Potential Benefits and Risks

• Neoadjuvant immunotherapy with pembrolizumab may offer potential benefits, including improved overall survival, increased pathologic complete response rates, and enhanced systemic immune responses 4, 5.
• However, the treatment is also associated with potential risks, including immune-related adverse events, such as thyroid dysfunction, hepatitis, and pneumonitis 3, 7.
• The patient's history of skin cancers, including SCC and BCC, may also impact the treatment decision, and careful consideration of the potential risks and benefits is necessary.