PD-1 Inhibitor Pregnancy: Contraindicated — PD-1 pathway critical for fetal immune tolerance; effective contraception during and for 4 months after treatment

Pembrolizumab (Head and Neck SCC)

Brand names: Keytruda

Adult dose

Dose: 200 mg IV every 3 weeks or 400 mg IV every 6 weeks

Route: Intravenous infusion over 30 minutes

Frequency: Every 3 weeks or every 6 weeks (flat dosing)

Max: 400 mg per dose (6-weekly)

R/M HNSCC first-line (CPS ≥1): pembrolizumab ± platinum/5-FU; CPS ≥20: pembrolizumab monotherapy; R/R after platinum: pembrolizumab monotherapy regardless of PD-L1; CPS testing required

Paediatric dose

Dose: Not established for HNSCC N/A/kg

Route: N/A

Frequency: N/A

Max: N/A

Paediatric HNSCC is exceptionally rare; pembrolizumab licensed for some paediatric indications (cHL)

Dose adjustments

Renal

No dose adjustment required

Hepatic

No dose adjustment required for mild-moderate impairment

Paediatric weight-based calculator

Patient weight (kg)

Paediatric HNSCC is exceptionally rare; pembrolizumab licensed for some paediatric indications (cHL)

Clinical pearls

KEYNOTE-048 (Burtness et al. NEJM 2019): pembrolizumab monotherapy superior OS to EXTREME regimen (cetuximab+platinum+5-FU) in CPS ≥20 R/M HNSCC (14.9 vs 10.7 months); pembrolizumab+chemotherapy superior in CPS ≥1; transformed first-line standard of care
PD-L1 CPS (combined positive score) = key biomarker: CPS ≥20 qualifies for pembrolizumab monotherapy; CPS 1-19 for combination; CPS <1 still uses platinum-based chemotherapy — companion diagnostic testing (PD-L1 IHC 22C3) mandatory
Head and neck SCC includes oral cavity, oropharynx (HPV+ and HPV-), larynx, hypopharynx, nasopharynx — prognosis and treatment vary by site; HPV+ oropharyngeal SCC has better prognosis and may respond differently to immunotherapy
Immune-related adverse events (irAEs): endocrinopathies (hypothyroidism 10-15%) rarely resolve — most patients require lifelong levothyroxine; checkpoint colitis, pneumonitis require systemic steroids; severe irAEs (grade 3-4) require permanent discontinuation
KEYNOTE-048 transformed EXTREME regimen practice: pembrolizumab now replaces cetuximab as the immunotherapy backbone in first-line R/M HNSCC; cetuximab_ent remains relevant in subsequent lines

Contraindications

Active severe autoimmune disease requiring immunosuppression
Known hypersensitivity

Side effects

Immune-mediated adverse events: pneumonitis, colitis, hepatitis, endocrinopathies (hypothyroidism most common), nephritis, dermatitis
Fatigue
Nausea
Infusion reactions

Interactions

Systemic corticosteroids — prophylactic/chronic use may reduce efficacy; use for irAE management only
Live vaccines — avoid

Monitoring

PD-L1 CPS testing before treatment
TFTs (every 3 months)
LFTs, creatinine, FBC (each cycle)
Chest imaging if respiratory symptoms
Endoscopy if colitis suspected
HbA1c (diabetes mellitus irAE)

Reference: BNFc; BNF 90; KEYNOTE-048 (Burtness et al. NEJM 2019); NICE TA670; MHRA SPC Keytruda; ESMO HNSCC Guidelines (2021). Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

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