KEYTRUDA® (pembrolizumab) plus chemotherapy in HNSCC

Prescribing Information (Great Britain) & Prescribing Information (Northern Ireland) [External links]

KEYTRUDA, in combination with platinum and 5-fluorouracil (5-FU) chemotherapy, is indicated for the first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) in adults whose tumours express PD-L1 with a CPS ≥ 11

Trial Design and Key Endpoints1,2

KEYNOTE-048 was a randomised, open-label, Phase III study of pembrolizumab monotherapy vs EXTREME and pembrolizumab plus chemotherapy vs EXTREME in patients with untreated locally incurable recurrent or metastatic HNSCC.


The recommended dose of KEYTRUDA in adults is either 200 mg every 3 weeks or 400 mg every 6 weeks administered as an intravenous infusion over 30 minutes.1

Overall Survival1

KEYTRUDA plus chemotherapy demonstrated clinically and statistically significant superiority in OS primary endpoint in CPS ≥ 1 population in KEYNOTE-048 when compared to EXTREME1

Figure adapted from KEYTRUDA (pembrolizumab) SmPC.

KEYTRUDA plus chemotherapy resulted in a 35% reduction in risk of death vs EXTREMEh,1

Progression Free Survival1

Table adapted from KEYTRUDA (pembrolizumab) SmPC.

PFS assessed per RECIST v1.1 by blinded independent central radiologic review.

Overall Response Rate & Duration of Response1–3

Endpoints were not powered for statistical comparison

Figure adapted from KEYTRUDA (pembrolizumab) SmPC.

Endpoints were not powered for statistical comparison

Figure adapted from Burtness B et al. Lancet. 2019 (suppl. appx.).

KEYTRUDA plus chemotherapy demonstrated a durable DoR in patients with PD-L1 expression CPS ≥12,3

Safety (as-treated population)2–4

KEYTRUDA plus chemotherapy demonstrated a comparable overall safety profile vs EXTREME4

Table adapted from Burtess B et al. Lancet 2019 supplementary appendix and the EMA assessment report for KEYTRUDA.

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For eligible patients, start with KEYTRUDA, the first anti-PD-1 therapy to be approved in 1L treatment of M/uR HNSCC in the UK1

KEYTRUDA plus chemotherapy vs EXTREME in the CPS ≥1 population:
Achieved clinical and statistical significance and superiority at OS primary endpointh 35% reduction in risk of death (HR 0.65; 95% CI; 0.53–0.80; p=0.00002).1
PFS (multiple primary end points) Statistical significance not met.2,4
Safety profilem Comparable safety profile.2,4
KEYTRUDA SmPC Dosing Fixed dose regimen Q3W (200 mg) intravenously over 30 minutes.1

IA2 data cutoff date: June 13 2018; FA data cutoff date: February 25, 2019.

For details on KEYNOTE-048 data, please see presentation available for download or view the SmPC: SmPC for Great Britain & SmPC for Northern Ireland [External links]

  • Data support KEYTRUDA with platinum and 5-FU chemotherapy as a first-line treatment option for M/uR HNSCC1,2
  • To prescribe KEYTRUDA, patients require timely PD-L1 testing and appropriate CPS evaluation


a Full trial data included all participants regardless of PD-L1 status. Data has been adapted to reflect CPS ≥1 population, as per KEYTRUDA license
b Assessed using the PD-L1 IHC 22C3 pharmDx assay (Agilent). TPS = % of tumour cells with membranous PD-L1 expression
c Assessed using the CINtec p16 histology assay (Ventana), cutpoint for positivity = 70%
d Following a loading dose of 400 mg/m2
e Assessed per RECIST v1.1 by blinded, independent review
f To be presented at a later date
g 400 mg Q6W dosing based on SmPC, not investigated in KEYNOTE-048
h 35% reduction: median follow-up of 13.0 months for KEYTRUDA plus chemotherapy1
i In patients with measurable disease per central review baseline. A further 26% of patients in the KEYTRUDA monotherapy arm and 33% of patients in the EXTREME arm had stable disease3
j All cause
k Adverse events (Grade 3–5) of any cause which occurred in ≥ 5 participants
l Adverse events of special interest, which were based on a list of prespecified list of preferred terms and are considered to be medically equivalent to the immune-mediated events and infusion-related reactions
m As-treated population


5-FU: 5 fluorouracil
AE: adverse event
AEOSI: adverse event of special interest
AUC 5: desired carboplatin exposure of area under curve 5 mg/m2
CI: confidence interval
CPS: combined positive score
CR: complete response
DoR: duration of response
ECOG: Eastern Cooperative Oncology Group
EORTC: European Organisation for Research and Treatment of Cancer
EXTREME: drug regimen consisting of Cetuximab 250 mg/m2 Q1W (following a loading dose of 400 mg/m2) + 5-FU 1000 mg/m2/d for 4 days + carboplatin AUC 5 or cisplatin 100 mg/m2 Q3W for 6 cycles
HNSCC: head and neck squamous cell carcinoma
HR: hazard ratio
HRQoL: health related quality of life
ITT: intention to treat
M/uR: metastatic or unresectable recurrent
OS: overall survival
ORR: objective response rate
PD-1: programmed cell death protein 1
PD-L1: programmed death-ligand 1
PFS: progression-free survival
PR: partial response
PS: performance status
QLQ: quality of life questionnaire
QxW: x-weekly dosing
R: randomised
RECIST: response evaluation criteria in solid tumours
R/M: recurrent or metastatic
SCC: squamous cell carcinoma
TPS: tumour proportion score


  1. KEYTRUDA Summary of Product Characteristics.
  2. Burtness B et al. Lancet. 2019:394;1915–28.
  3. Burtness B et al. Lancet. 2019:394; 1915-28 (suppl. appx.).
  4. EMA, assessment report for KEYTRUDA. EMEA/H/C/003820/II/0065. October 2019. Available from:

Supporting documentation

Prescribing Information (Great Britain) & Prescribing Information (Northern Ireland)
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GB-OHN-00354 | Date of Preparation: September 2021