Can a 64‑year‑old patient with acceptable health, organ function, and comorbidities tolerate pembrolizumab‑based immunotherapy, including the neoadjuvant regimen used in SWOG S1801?

Can a 64-Year-Old Patient Tolerate Pembrolizumab-Based Immunotherapy?

Yes, a 64-year-old patient with acceptable health, organ function, and comorbidities can safely tolerate pembrolizumab-based immunotherapy, including the neoadjuvant regimen used in SWOG S1801, as age alone does not predict increased toxicity or reduced efficacy. 1

Age-Specific Safety Data

Geriatric Population Evidence

• No overall differences in safety or effectiveness were observed between elderly patients (≥65 years) and younger patients across multiple pembrolizumab trials in melanoma, NSCLC, HNSCC, and urothelial carcinoma. 1

• In the FDA prescribing information, 48% of 3,781 patients treated with pembrolizumab across these indications were ≥65 years, and 17% were ≥75 years, demonstrating extensive real-world experience in older adults. 1

• The SWOG S1801 trial specifically showed that grade ≥3 treatment-related adverse events occurred in only 12% of patients receiving neoadjuvant-adjuvant pembrolizumab, with no age-specific safety concerns identified. 2, 3

Important Age-Related Caveats

• Patients ≥75 years treated with pembrolizumab in combination with enfortumab vedotin experienced higher rates of fatal adverse reactions (7% vs 4% in younger patients), but this applies to combination therapy, not pembrolizumab monotherapy. 1

• In classical Hodgkin lymphoma, patients ≥65 years had a higher incidence of serious adverse reactions (50%) compared to those <65 years (24%), though this represents a different disease context than melanoma. 1

Neoadjuvant Pembrolizumab Regimen Tolerability

SWOG S1801 Safety Profile

• The neoadjuvant-adjuvant pembrolizumab approach (3 preoperative + 15 postoperative doses) demonstrated comparable toxicity to adjuvant-only therapy (12% vs 14% grade ≥3 treatment-related adverse events). 2, 3

• This regimen involves pembrolizumab 200 mg IV every 3 weeks for a maximum of 3 preoperative courses, followed by surgery, then 15 additional postoperative courses. 2

• The total pembrolizumab exposure is identical between neoadjuvant-adjuvant and adjuvant-only approaches, meaning no additional cumulative toxicity burden. 4

Guideline Recommendations for Older Adults

ASCO 2023 Melanoma Guidelines

• ASCO strongly recommends up to 3 neoadjuvant pembrolizumab courses followed by surgery and 15 adjuvant courses for clinical stage IIIB-IV resectable melanoma, with no age-based restrictions. 2, 4

• Treatment individualization is recommended based on risk-benefit assessment, but this applies to disease stage and comorbidities, not chronological age alone. 2

ESMO 2024 Breast Cancer Guidelines (Applicable Principles)

• Treatment of elderly patients should be adapted to biological age (not chronological age), with consideration of less aggressive regimens only in frail patients. 2

• In patients suitable for standard therapy, a standard multidrug regimen should be used regardless of age. 2

• A geriatric assessment should be carried out before making treatment decisions to identify frailty rather than relying on age cutoffs. 2

Practical Clinical Algorithm for the 64-Year-Old Patient

Step 1: Assess Functional Status and Comorbidities

• Evaluate performance status (ECOG 0-1 preferred for full-dose therapy). 2
• Screen for autoimmune conditions, chronic infections, or organ dysfunction that would contraindicate immunotherapy. 2
• Consider geriatric assessment tools if concerns about frailty exist, though at age 64 this is rarely necessary. 2

Step 2: Monitor for Immune-Related Adverse Events

• Patients receiving pembrolizumab must be monitored very closely for immune-related adverse events throughout treatment, following ESMO guidelines for immunotherapy toxicity management. 2

• Common immune-related toxicities include pneumonitis, colitis, hepatitis, endocrinopathies, and dermatologic reactions, which occur at similar rates regardless of age. 1

Step 3: Proceed with Standard Dosing

• Use pembrolizumab 200 mg IV every 3 weeks without dose reduction based on age alone. 2, 1

• Alternative dosing of 400 mg IV every 6 weeks is FDA-approved and may offer logistical advantages without compromising safety or efficacy. 1

Common Pitfalls to Avoid

• Do not withhold or dose-reduce pembrolizumab based solely on chronological age of 64 years, as this represents arbitrary age discrimination without evidence basis. 1

• Do not delay surgery beyond 12 weeks from neoadjuvant therapy initiation, as this may compromise outcomes. 4

• Do not assume that older patients cannot tolerate immunotherapy—the data show equivalent tolerability across age groups in melanoma trials. 1, 3

• Be vigilant for immune-related adverse events but recognize these occur at similar rates in older and younger patients receiving pembrolizumab monotherapy. 1