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KEYTRUDA® (pembrolizumab) in combination with platinum- and fluoropyrimidine-based chemotherapy, is indicated for the first-line treatment of patients with locally advanced or metastatic carcinoma of the esophagus or gastroesophageal junction (GEJ).1

Superior Overall Survival2 :

Reduction in the risk of death

with KEYTRUDA + Cisplatin + 5-fluorouracil (5-FU) compared to Placebo + Cisplatin + 5-fluorouracil
(5-FU) alone

(HRa=0.73; 95% CI, 0.62–0.86; Pb<0.0001)

Median OSc:

Events observed1:

aBased on the stratified Cox proportional hazard model.1
bBased on a stratified log-rank test.1
cBased on Kaplan-Meier estimation.

In KEYNOTE-5902,

KEYTRUDA can be used with your choice of platinum-/ fluoropyrimidine-based chemotherapy for certain locally advanced or metastatic esophageal or GEJ cancers1

GEJ = gastroesophageal junction; 5-FU = 5-fluorouracil; HR = hazard ratio; CI = confidence interval; OS = overall survival.

References:

  1. KEYTRUDA Prescribing Information
  2. Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima, el al;Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021 Aug 28;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4. Erratum in: Lancet. 2021 Nov 20;398(10314):1874. PMID: 34454674.
  3. American Cancer Society. What Is Esophagus Cancer? 2020. Accessed 26th November 2024 https://www.cancer.org/cancer/esophagus-cancer/about/what-is-cancer-of-the-esophagus.html.
  4. Marieb EN, Hoehn K. The digestive system. In: Human Anatomy & Physiology. 11th ed. New Jersey: Pearson Education; 2019:869-925.
  5. Schneider PM, Ménig SP. Siewert classification of adenocarcinoma of the esophagogastric junction: still in or already out? In: Giacopuzzi S, Zanoni A, de Manzoni G, ed. Adenocarcinoma of the Esophagogastric Junction: From Barrett’s Esophagus to Cancer. Switzerland: Springer International Publishing; 2017:47-56.

Study Arms

Randomized, placebo-controlled, double-blind, phase 3 study across 168 medical centres in 26 countries1

Efficacy Outcomes1

  • The major efficacy outcome measures were OS and PFS as assessed by the investigator according to RECIST v1.1.
  • Secondary efficacy outcome measures were ORR and DOR, according to RECIST v1.1, as assessed by the investigator.

aAll patients were required to have tumor specimens for PD-L1 testing at a central laboratory; PD-L1 status was determined using the PD-L1 IHC 22C3 pharmDxTM kit.1
bOr per local standard for 5-FU administration, for up to 24 months.2
cSaline I.V Q3W for ≤35 cycles. All treatments were continued for the specified number of cycles or until disease progression, intolerable toxicity, withdrawal of consent, or physician decision; Data cutoff: July 2, 20201
dTreatment was continued until disease progression, unacceptable toxicity, illness, physician or patient decision to withdraw, non- compliance, completion of 35 cycles, complete response, or discontinuation for administrative reasons. Disease progression was verified by central imaging review. During follow-up, survival was assessed every 12 weeks.1

The baseline characteristics were2

  • Median age of 63 years (range: 27 to 94)
  • 43% age 65 or older
  • 83% male
  • 37% White and 53% Asian
  • 40% had an ECOG PS of 0 and 60% had an ECOG PS of 1
  • 91% had M1 disease and 9% had M0 disease
  • 73% had a tumor histology of squamous cell carcinoma, and 27% had adenocarcinoma.

DOR = duration of response; ECOG = Eastern Cooperative Oncology Group; ESCC = esophageal squamous cell carcinoma; GEJ = gastroesophageal junction; PD-L1 = programmed death ligand 1; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors v1.1. OS = overall survival; PFS = progression-free survival; ORR = objective response rate; HER2 = Human Epidermal Growth Factor Receptor 2; 5-FU = 5-fluororacil; Q3W = every 3 weeks; IV = intravenous.

References:

  1. Sun JM, Shen L, Shah MA, Enzinger P, et al; KEYNOTE-590 Investigators. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021 Aug 28;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4. Erratum in: Lancet. 2021 Nov 20;398(10314):1874. PMID: 34454674.
  2. KEYTRUDA Prescribing Information

Reduction in the risk of death

(HRa=0.73 (95% CI, 0.62–0.86); Pb<0.0001) in all randomized patients

Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-590

Adapted from Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima, el al. Lancet. 2021 Aug 28;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4.

OS rate

24-Month OS Rate1

After 24 months of treatment, the overall survival rate for patients in the KEYTRUDA + cisplatin + 5-fluorouracil (5-FU) group was 28%, whereas it was 16% in the Placebo + cisplatin + 5-fluorouracil (5-FU) group. This demonstrates a sustained advantage for the KEYTRUDA + cisplatin + 5-fluorouracil (5-FU) combination therapy.

Median OS1

The median overall survival for patients who received KEYTRUDA + cisplatin + 5-fluorouracil (5-FU) was 12.4 months, with a 95% CI. In contrast, patients treated with Placebo + cisplatin + 5-fluorouracil (5-FU) had a median overall survival of 9.8 months. This indicates a substantial extension in survival with the KEYTRUDA + cisplatin + 5-fluorouracil (5-FU) combination therapy.

Median OS (95% CI)c

Events observed2

aBased on the stratified Cox proportional hazard model.2
bBased on a stratified log-rank test.2
cBased on Kaplan-Meier estimation.2

DOR = duration of response; ECOG = Eastern Cooperative Oncology Group; PD-L1 = programmed death ligand 1; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors v1.1.

KEYTRUDA (pembrolizumab) in combination with platinum- and fluoropyrimidine-based chemotherapy, is indicated for the first-line treatment of patients with locally advanced or metastatic carcinoma of the esophagus or gastroesophageal junction (GEJ).

References:

  1. Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima, el al; Supplementary appendix to KEYNOTE-590 Investigators. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021 Aug 28;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4. Erratum in: Lancet. 2021 Nov 20;398(10314):1874. PMID: 34454674.
  2. KEYTRUDA Prescribing Information

Reduction in the risk of disease progression

HRb=0.65 (95% CI, 0.55-0.76);Pc <0.0001 in all randomized patients

Adapted from Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima, el al. Lancet. 2021 Aug 28;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4.

PFS rate

Significant improvement in progression-free survival rates and were consistently higher in the KEYTRUDA + cisplatin + 5-fluorouracil (5-FU) group than in the Placebo + cisplatin + 5-fluorouracil (5-FU) for patients with esophageal squamous cell carcinoma (HR 0.65 [95% CI 0.55–0.76]; p<0.0001) in all randomised patients, and by 12 months and 18 months

Median PFS (95% CI)d

Events observed2

aAssessed by investigator using RECIST v1.1.
bBased on stratified Cox proportional hazard model.
cBased on stratified log-rank test.
dBased on Kaplan-Meier estimation.

CI = Confidence interval; HR = Hazard ratio; PD-L1 = programmed death ligand 1; CPS = Combined Positive Score;

References:

  1. Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima, el al; Supplementary appendix to KEYNOTE-590 Investigators. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021 Aug 28;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4. Erratum in: Lancet. 2021 Nov 20;398(10314):1874. PMID: 34454674.
  2. KEYTRUDA Prescribing Information

ORR and DOR with KEYTRUDA + cisplatin/5-FU vs cisplatin/5-FU alone1

aAssessed by investigators using RECIST v1.1.
bOne-sided p value for testing.
cBased on patients with a best overall response as confirmed complete or partial response.
dBased on Kaplan-Meier method for censored data.

ORR = objective response rate; DOR = duration of response; CR = complete response; PR = partial response; RECISTv1.1 = Response Evaluation Criteria in Solid Tumors.

In the first-line treatment of certain locally advanced or metastatic esophageal or GEJ cancers KEYTRUDA + platinum-/fluoropyrimidine-based chemotherapy may be an option for your appropriate patients2

References:

  1. Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima, el al; Supplementary appendix to KEYNOTE-590 Investigators. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021 Aug 28;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4. Erratum in: Lancet. 2021 Nov 20;398(10314):1874. PMID: 34454674.
  2. KEYTRUDA Prescribing Information

Choose between 2 dosing options for KEYTRUDA, and your choice of platinum-/ fluoropyrimidine-based chemotherapy

KEYTRUDA Dosing1

  • KEYTRUDA 200 mg with Cisplatin 80 mg/m2 I.V on Day 1 of each 3-week cycle for up to 6 cycles + 5-FU 800 mg/m2 I.V per day on Day 1 to Day 5 of each 3-week cycle (or per local standard for 5-FU administration) for up to 24 months.
  • Chemotherapy: Cisplatin 80 mg/m2 I.V on Day 1 of each 3-week cycle for up to 6 cycles + 5-FU 800 mg/m2 I.V per day on Day 1 to Day 5 of each 3-week cycle (or per local standard for 5-FU administration) for up to 24 months.
  • Administer KEYTRUDA prior to chemotherapy when given on the same day.

aUntil disease progression, unacceptable toxicity, or up to 24 months
bDay 1 of each three-week cycle for up to six cycles
cDay 1 to Day 5 of each three-week cycle, or per local standard for 5-FU administration

Which dosing regimen of KEYTRUDA is appropriate for your patient with certain advanced esophageal or GEJ cancers?

Treatment related adverse events in intention to treat population*

Adverse events of special interest**

  • The as-treated population included all patients who were randomly assigned to a treatment group and received at least one dose of study treatment.
  • *Treatment-related adverse events with incidence of 5% or higher in any group are shown; treatment-related grade 5 events included febrile neutropenia, diarrhoea, multiple organ dysfunction, hepatic failure, pneumonia, acute kidney injury, interstitial lung disease, pneumonitis, and pulmonary embolism, which each occurred in one patient in the pembrolizumab plus chemotherapy group, and febrile neutropenia, death, multiple organ dysfunction syndrome, sepsis, and interstitial lung disease, which each occurred in one patient in the placebo plus chemotherapy group.
  • ** Immune-mediated adverse events and infusion reactions were based on a list of terms specified by the sponsor, regardless of attribution to any study treatment by investigators.

5-FU = 5-fluorouracil; IV = intravenous; mg = milligram; Q3W = every 3 weeks; Q6W = every 6 weeks.

Consider KEYTRUDA for your appropiate patients

References:

  1. KEYTRUDA Prescribing Information
  2. Sun JM, Shen L, Shah MA, Enzinger P, et al; KEYNOTE-590 Investigators. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021 Aug 28;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4. Erratum in: Lancet. 2021 Nov 20;398(10314):1874. PMID: 34454674.

BH-KEY-00083 | Expiry Date: 08-10-2026