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KEYTRUDA® (pembrolizumab) plus chemotherapy in metastatic non-squamous NSCLC

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

Discover the 4 year follow-up data from KEYNOTE-189*

KEYNOTE-189 study design1
The original analysis1

A randomised, multicentre, double-blind, active-controlled, phase 3 trial in patients (n=616) with previously untreated metastatic non-squamous NSCLC with no EGFR or ALK positive mutations.1

616 patients were randomly assigned (in a 2:1 ratio) to receive pemetrexed and a platinum based drug plus either 200 mg of pembrolizumab (n=410) or placebo every 3 weeks for 4 cycles (n=210), followed by placebo or pembrolizumab for up to a total of 35 cycles plus pemetrexed maintenance therapy.1

Overall Survival and Progression-Free Survival were primary endpoints. Secondary endpoints consisted of Overall Response Rate, Duration of Response, and Safety.1

The results of this phase 3 trial were first published with a median follow-up of 10.5 months.1
The latest follow-up was published with a median follow up of 46.3 months.2

KEYTRUDA plus chemotherapy (pemetrexed and platinum) provides superior survival vs. plat-pem for the first-line treatment of metastatic non-squamous NSCLC in adults with no EGFR/ALK positive mutations:1

  • Superior OS with a 51% reduction in the risk of death (HR 0.49, p<0.001)
  • Superior PFS with a 48% reduction in the risk of progression or death (HR 0.52, p<0.001)
  • Survival benefit observed in each of the PD-L1 subgroups including the <1% and 1-49% expressers*
  • Superior ORR (47.6% vs 18.9%, p<0.001) and improved DOR
  • A generally manageable tolerability profile. The frequency of adverse events for the combination was observed to be higher than for each agent alone, reflecting the contributions of each agent1,3

*Exploratory endpoints – no statistical conclusions can be drawn from them.

At a median follow-up of 46.3 months, KEYTRUDA plus chemotherapy (pemetrexed and platinum) continued to provide long-term survival benefit vs. plat-pem for the first-line treatment of metastatic non-squamous NSCLC in adults with no EGFR/ALK positive mutations:2

3-year OS rate nearly doubled
numerically
31.3% vs. 17.4%
for chemotherapy alone

(HR 0.60, p not tested)

Median OS more than doubled
numerically
22 months vs. 10.6 months
with chemotherapy alone

(p not tested)

Survival benefit observed in each of the PD-L1 TPS subgroups, including the PD-L1 TPS <1% expressers:
3-year OS rate of
23.3% vs. 5.3%
for chemotherapy alone†2

(HR 0.52, p not tested)

ORR more than doubled numerically
48.3% vs. 19.9%
and improved DOR

(p not tested)

A generally manageable tolerability profile. The frequency of adverse events for combination was comparable to previous studies. An increase in the frequency of Immune-mediated AEs and infusion reactions was observed in patients who received 35 cycles of KEYTRUDA.1-3

The recommended dose of KEYTRUDA as part of combination therapy is either 200 mg every 3 weeks or 400 mg every 6 weeks administered intravenously over 30 minutes. KEYTRUDA should be administered first when given in combination with chemotherapy.3

Exploratory endpoints - no statistical conclusions can be drawn from them.

Explore our related resources

NICE guidance
SMC guidance
Licensed indication

Pembrolizumab, with pemetrexed and platinum chemotherapy, is recommended as an option for untreated, metastatic, non-squamous non-small-cell lung cancer (NSCLC) in adults whose tumours have no epidermal growth factor receptor (EGFR)- or anaplastic lymphoma kinase (ALK)- positive mutations, only if pembrolizumab is stopped at 2 years of uninterrupted treatment or earlier if the disease progresses, and the company provides pembrolizumab according to the commercial arrangement.4

Pembrolizumab is accepted for restricted use within NHS Scotland in combination with pemetrexed and platinum chemotherapy, for the first-line treatment of metastatic non-squamous non-small-cell lung carcinoma (NSCLC) in adults whose tumours have no EGFR or ALK positive mutations and whose tumours express programmed death ligand 1 (PD-L1) with a <50% tumour proportion score (TPS), or in those whom it has not been possible to evaluate PD-L1 TPS.5

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first‑line treatment of metastatic non-squamous NSCLC in adults whose tumours have no EGFR or ALK positive mutations.3

The recommended dose of KEYTRUDA as part of combination therapy is 200 mg Q3W administered intravenously over 30 minutes. KEYTRUDA should be administered first when given in combination with chemotherapy.3

Q3W = Every three weeks; Q6W = Every six weeks.

Find out more about KEYTRUDA in mNSCLC

KEYTRUDA KEYNOTE-407

KEYTRUDA KEYNOTE-024

Patient management

References

  1. Gandhi L, et al. N Engl J Med 2018: 378: 2078-2092.
  2. Gray JE, et al. Presented at the 2020 World Conference on Lung Cancer (WCLC), January 28–31, 2021.
  3. KEYTRUDA Summary of Product Characteristics.
  4. National Institute for Health and Care Excellence (2021). Final appraisal determination: Pembrolizumab with pemetrexed and platinum-based chemotherapy for untreated non-small-cell lung cancer (CDF Review of TA557) [ID1584] Available from: https://www.nice.org.uk/guidance/indevelopment/gid-ta10529. NICE guidance is prepared for the National Health Service in England, and is subject to regular review and may be updated or withdrawn. NICE has not checked the user of its content in this document to confirm that it accurately reflects the NICE publication from with it is taken.to confirm that it accurately reflects the NICE publication from with it is taken.
  5. Scottish Medicines Consortium (2019). Appraisal determination: Pembrolizumab 25mg/mL concentrate for solution for infusion and 50mg powder for concentrate for solution for infusion (KEYTRUDA®). Available from: https://www.scottishmedicines.org.uk/medicines-advice/pembrolizumab-keytruda-resub-smc2207/.

Supporting documentation

Prescribing Information (Great Britain) & Prescribing Information (Northern Ireland)
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GB-PDO-01641 | Date of Preparation: August 2021