What is the role of immunotherapy, such as pembrolizumab (pembrolizumab) or nivolumab (nivolumab), in the treatment of an elderly patient with locally advanced buccal carcinoma and potential comorbidities?

Role of Immunotherapy in Elderly Patients with Locally Advanced Buccal Carcinoma

For elderly patients with locally advanced buccal carcinoma not amenable to curative surgery or radiotherapy, pembrolizumab monotherapy is the standard first-line treatment if the tumor is PD-L1 positive (CPS ≥1), while pembrolizumab plus platinum/5-FU is standard for PD-L1-negative tumors. 1

Treatment Algorithm Based on PD-L1 Status and Prior Therapy

First-Line Treatment (No Prior Platinum Therapy in Last 6 Months)

PD-L1-Positive Tumors (CPS ≥1):

• Pembrolizumab monotherapy is the preferred standard treatment with Level I, Grade A evidence and ESMO-MCBS score of 4 (highest clinical benefit) 1
• This approach avoids platinum-related toxicities (myelosuppression, nephrotoxicity, ototoxicity) that are particularly problematic in elderly patients with comorbidities 1

PD-L1-Negative Tumors (CPS <1):

• Pembrolizumab plus platinum/5-FU is the standard treatment with Level I, Grade A evidence 1
• Alternative: Platinum/5-FU/cetuximab if immunotherapy is contraindicated and patient is fit for platinum-based therapy 1
• For patients unfit for platinum: methotrexate, taxane, or cetuximab with best supportive care 1

After Platinum-Based Chemotherapy Within Last 6 Months

If Immunotherapy-Naïve:

• Standard: Platinum/5-FU/cetuximab with Level I, Grade A evidence 1

If Prior Immunotherapy:

• Nivolumab or pembrolizumab are both standard options with Level I, Grade A evidence and ESMO-MCBS score of 4 1
• Alternative if immunotherapy contraindicated: taxane, methotrexate, or cetuximab with best supportive care 1

Critical Considerations for Elderly Patients

Performance Status Assessment:

• Patients with good performance status (PS 0-1) can receive standard immunotherapy regimens 1
• Patients with PS 2 may receive single-agent immunotherapy or best supportive care depending on functional status and comorbidities 1
• Patients with PS 3-4 should receive best supportive care only 1

Safety Profile in Elderly:

• No overall differences in safety or effectiveness of pembrolizumab were observed between elderly patients (≥65 years) and younger patients in head and neck squamous cell carcinoma trials 2
• Elderly patients with classical Hodgkin lymphoma treated with pembrolizumab had higher incidence of serious adverse reactions (50% vs 24% in younger patients), warranting closer monitoring 2
• Nivolumab showed no overall safety differences between elderly and younger patients with head and neck squamous cell carcinoma 3

Immunotherapy Advantages Over Chemotherapy in Elderly:

• Immunotherapy has less bone marrow suppression compared to chemotherapy, reducing infection risk during the COVID-19 era and beyond 4
• Quality of life may be prioritized with immunotherapy, potentially avoiding morbid surgery in carefully selected geriatric patients 5

Evidence for Clinical Response

Efficacy Data:

• Durable complete clinical and radiologic responses have been documented in geriatric patients with gingival squamous cell carcinoma treated with pembrolizumab, with ongoing responses at 19 months 5
• Partial responses with minimal side effects have been observed in elderly patients at 5-9 months of treatment 5
• Pembrolizumab can induce regression of both squamous cell carcinoma and concurrent basal cell carcinoma, with complete response observed after 7-11 courses 6

Common Pitfalls and Contraindications

When to Avoid Immunotherapy:

• Active autoimmune disease requiring systemic immunosuppression is a contraindication 1
• Severe immune-related adverse events from prior immunotherapy 1
• In these cases, use platinum/5-FU/cetuximab if fit for platinum, or single-agent chemotherapy (methotrexate, taxane) or cetuximab with best supportive care if unfit 1

PD-L1 Testing Requirements:

• PD-L1 testing by Combined Positive Score (CPS) is mandatory to guide first-line treatment selection 1
• CPS ≥1 qualifies for pembrolizumab monotherapy; CPS <1 requires combination with chemotherapy 1, 7

Surgical Considerations:

• Neoadjuvant pembrolizumab does not increase postoperative adverse events compared to standard-of-care surgery, with similar rates of wound complications, flap failure, and return to operating room 8
• Trismus was actually lower in the pembrolizumab group (22% vs 50%, difference 28.1%) 8

Monitoring and Duration

Treatment Duration:

• Continue immunotherapy until disease progression, unacceptable toxicity, or up to 24 months in responding patients 2
• Pembrolizumab dosing: 200 mg IV every 3 weeks or 400 mg IV every 6 weeks 2
• Nivolumab dosing options exist for every 2-week or 4-week administration 3

Response Assessment:

• Clinical and radiologic assessment should occur every 6-9 weeks initially 1
• Immune-related response patterns may show initial pseudoprogression before response 9