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KEYTRUDA monotherapy in HNSCC
KEYTRUDA (pembrolizumab) HNSCC /
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KEYTRUDA® (pembrolizumab) in first-line head & neck squamous cell carcinoma (HNSCC)

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

KEYTRUDA as monotherapy is indicated for the first-line treatment of metastatic or unresectable recurrent (M/uR) HNSCC in adults whose tumours express PD-L1 with a CPS ≥ 1.1

KEYTRUDA monotherapy for your M/uR HNSCC patients with PD-L1 expression of CPS ≥ 1

With KEYTRUDA monotherapy in the KEYNOTE-048 trial…

More than 1 in 4 patients were alive at 2 years1,2
PFS was not significantly different vs EXTREME3
There was a sustained response, with a median duration of 2 years2
The overall safety profile was favourable vs EXTREME, with the exception of hypothyroidism and pneumonitis1,2

Click on each tab below to explore data from the KEYNOTE-048 final analysis and 4-year post-hoc analysis:

KEYNOTE-048
study design
KEYNOTE-048
final analysis
– efficacy
KEYNOTE-048
final analysis
– safety
KEYNOTE-048
4-year post-hoc
analysis

KEYNOTE-048 original study design: KEYTRUDA ± chemotherapy vs EXTREME1,3

Multi-centre, randomised, open-label, active-controlled Phase III study

KEYNOTE 048 study design including KEYTRUDA monotherapy, KEYTRUDA plus chemotherapy and EXTREME with list of key endpoints

Figure adapted from references 1 to 4. aAssessed using the PD-L1 IHC 22C3 pharmDx assay (Agilent). TPS = % of tumour cells with membranous PD-L1 expression. bAssessed using the CINtec p16 histology assay (Ventana), cutpoint for positivity = 70%. cFollowing a loading dose of 400 mg/m2; after completion of platinum agent and 5-FU, cetuxumab could be continued until PD for patients with stable disease. dCarboplatin AUC 5 OR cisplatin 100 mg/m2 + 5-FU 1000 mg/m2/day for 4 days for 6 cycles of 3 weeks.

Overall survival Progression-free survival Overall response rate Duration of response

Overall survival with KEYTRUDA monotherapy at 2 years in the CPS ≥ 1 population vs EXTREME2

More than 1 in 4 patients were alive at 2 years.2

Kaplan-Meier curve of overall survival for HNSCC patients in KEYNOTE 048, KEYTRUDA (pembrolizumab) vs EXTREME

KEYTRUDA monotherapy resulted in a significantly longer overall survival vs EXTREME and a 26% reduction in the risk of death.2

Progression-free survival with KEYTRUDA monotherapy at 2 years in the CPS ≥ 1 population vs EXTREME1,3

PFS was not significantly different vs EXTREME.1,3

Table of progression-free survival in for HNSCC patients in KEYNOTE 048, KEYTRUDA (pembrolizumab) vs EXTREME

Overall response rate with KEYTRUDA monotherapy at 2 years in the CPS ≥ 1 population vs EXTREME2

Almost 1 in 5 patients had a complete or partial response to KEYTRUDA, with a median follow-up of 11.5 months.2

A further 28% of patients in the KEYTRUDA monotherapy arm and 33% of patients in the EXTREME arm had stable disease.2

Bar chart of overall response rates for HNSCC patients in KEYNOTE 048 for KEYTRUDA (pembrolizumab) and EXTREME, including complete response rates and partial response rates

Duration of response with KEYTRUDA monotherapy at 2 years in the CPS ≥ 1 population vs EXTREME2

There was a sustained response with KEYTRUDA monotherapy,
with a median of 2 years.2

Kaplan-Meier curve of duration of response for HNSCC patients in KEYNOTE 048 for KEYTRUDA (pembrolizumab) vs EXTREME

Secondary and exploratory endpoints were not powered for statistical comparison

Adverse events (AE) Adverse events of special interest (AEOSI)

Adverse events with KEYTRUDA monotherapy at 2 years in the as-treated population* vs EXTREME2

The overall safety profile for KEYTRUDA was favourable vs EXTREME, with the exception of hypothyroidism and pneumonitis.2

Table of adverse events for HNSCC patients in KEYNOTE 048 for KEYTRUDA (pembrolizumab) vs EXTREME

Risk difference for adverse events of any cause with incidence ≥15%2

Table of risk difference for adverse events for HNSCC patients in KEYNOTE 048 with KEYTRUDA (pembrolizumab) vs EXTREME

Adverse events of special interest (AEOSI)

Table of adverse events of special interest for HNSCC patients in KEYNOTE 048 for KEYTRUDA (pembrolizumab) vs EXTREME
Bar chart of incidence of adverse events of special interest for HNSCC patients in KEYNOTE 048 for KEYTRUDA (pembrolizumab) vs EXTREME

Learn more about the management of immune-related adverse events with KEYTRUDA

Link to slide deck - a guide to KEYTRUDA (pembrolizumab) and how to manage immune-related adverse events
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A guide to KEYTRUDA® (pembrolizumab) and how to manage immune-related adverse events

 

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

Overall survival Overall response rate Duration of response Treatment-related adverse events

Overall survival with KEYTRUDA monotherapy at 4 years in the CPS ≥ 1 population vs EXTREME5

Post-hoc analyses were not powered for statistical comparison

1 in 6 patients were alive at 4 years with KEYTRUDA vs 1 in 17 with EXTREME5

Kaplan-Meier curve of overall survival for HNSCC patients at 4 years in KEYNOTE 048 with KEYTRUDA (pembrolizumab) vs EXTREME

Overall response rate with KEYTRUDA monotherapy at 4 years in the CPS ≥ 1 population vs EXTREME5

Post-hoc analyses were not powered for statistical comparison

Bar chart of overall response rates for HNSCC patients at 4 years in KEYNOTE 048 for KEYTRUDA (pembrolizumab) vs EXTREME

Duration of response with KEYTRUDA monotherapy at 4 years in the CPS ≥ 1 population vs EXTREME5

Post-hoc analyses were not powered for statistical comparison

Kaplan-Meier curve of duration of response for HNSCC patients at 4 years in KEYNOTE 048 for KEYTRUDA (pembrolizumab) vs EXTREME

Treatment-related adverse events (TRAEs) with KEYTRUDA monotherapy at 4 years in the as-treated population* vs EXTREME5

TRAEs remained consistent with known safety profiles5

Table of treatment-related adverse events for HNSCC patients at 4 years in KEYNOTE 048 for KEYTRUDA (pembrolizumab) vs EXTREME

Safety data originates from the total population and could
not be separated by PD-L1 expression levels.

*As-treated population = all patients who received at least one dose of allocated treatment.5

Learn more about the management of immune-related adverse events with KEYTRUDA

Link to slide deck - a guide to KEYTRUDA (pembrolizumab) and how to manage immune-related adverse events
Rating

A guide to KEYTRUDA® (pembrolizumab) and how to manage immune-related adverse events

 

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

To find out more about the different types of patients who could benefit from KEYTRUDA, arrange a discussion with an MSD representative

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Discover all the data for KEYTRUDA monotherapy in M/uR HNSCC

KEYNOTE 048 slide deck on KEYTRUDA (pembrolizumab) plus or minus chemotherapy vs EXTREME in first-line HNSCC
Rating

Discover all the data for KEYTRUDA in M/uR HNSCC (KEYNOTE-048 full results slide deck)

 

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

KEYTRUDA dosing information

With two options available, choose the appropriate dosing regimen for your patients1,3

KEYTRUDA alone or in combination with chemotherapy

IV bag and calendar icons - KEYTRUDA (pembrolizumab) dosing schedule is 200 mg every 3 weeks or 400 mg every 6 weeks

Both doses are administered as IV infusions over 30 minutes

The study that led to the approval of the Q6W for monotherapy and combination patients assessed the 400 mg Q6W dosing schedule based on an exposure-response evaluation using modelling and simulation. It concluded that 400 mg Q6W dosing regimen for KEYTRUDA monotherapy and combination is predicted to have a similar efficacy and safety profile as the approved 200 mg Q3W dosing regimen.

PD-L1 testing supports a targeted treatment approach for all appropriate patients with M/uR HNSCC*1

CPS ≥ 1 in the KEYNOTE-048 study1

Icons representing the 85% of patients with HNSCC in KEYNOTE 048 who had tumours expressing PD-L1 with a CPS ≥ 1

85%

(n=754/882) of treatment-naïve patients with M/uR HNSCC had tumours that expressed PD-L1 (CPS ≥ 1)3,6

*The KEYNOTE-048 study employed the PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies, Carpinteria, CA, USA)1,6

KEYNOTE-048 trial was a multi-centre, randomised, open-label, active-controlled Phase III study.

KEYTRUDA monotherapy; EXTREME n=255.

Abbreviations

5-FU, 5-fluorouracil; AE, adverse event; AEOSI, adverse events of special interest; AUC 5, desired carboplatin exposure of 5 mg/ml; CI, confidence interval; CPS, combined positive score; CR, complete response; DoR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; ESMO, European Society for Medical Oncology; EXTREME, cetuximab + 5-fluorouracil + platinum-based chemotherapy; HNSCC, head and neck squamous cell carcinoma; HR, hazard ratio; IHC, immunohistochemistry; ITT, intention to treat; IV, intravenous; mo, month; M/uR, metastatic or unresectable recurrent; No., number; NR, not reported; ORR, objective response rate; OS, overall survival; P16, cyclin-dependent kinase inhibitor 2A; PD, progressive disease; PD-1, programmed cell death-1; PD-L1, programmed death ligand-1; PFS, progression-free survival; PFS2, time from randomisation to objective tumour progression on next-line treatment or death from any cause; PR, partial response; Q1W, every week; Q3W, every 3 weeks; Q6W, every 6 weeks; QoL, quality of life; R, randomised; RECIST, Response Evaluation Criteria in Solid Tumours; SCC, squamous cell carcinoma; TPS, tumour proportion score; TRAE, treatment-related adverse events.

References

  1. KEYTRUDA (pembrolizumab) Summary of Product Characteristics.
  2. Burtness B et al. Lancet 2019:394;1915–28 (suppl. appx.).
  3. Burtness B et al. Lancet 2019:394;1915–28.
  4. Harrington K et al. Presented at American Society of Clinical Oncology (ASCO) Annual Meeting 2020. 29 May–2 June 2020.
  5. Greil R et al. Presented at ESMO Virtual Congress 2020; 19–21 September 2020.
  6. Agilent. PD-L1 IHC 22C3 pharmDx Interpretation Manual – HNSCC

GB-OHN-00357 | Date of Preparation: November 2021