FAQs

Melanoma¹

KEYTRUDA as monotherapy is indicated for the treatment of advanced (unresectable or metastatic) melanoma in adults.

KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults with Stage III melanoma and lymph node involvement who have undergone complete resection.

Non-small cell lung carcinoma (NSCLC)¹

KEYTRUDA as monotherapy is indicated for the first-line treatment of metastatic non-small cell lung carcinoma in adults whose tumours express PD-L1 with a ≥ 50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations.

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

KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of metastatic squamous non-small cell lung carcinoma in adults..

KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic non-small cell lung carcinoma in adults whose tumours express PD-L1 with a ≥ 1% TPS and who have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumour mutations should also have received targeted therapy before receiving KEYTRUDA.

Classical Hodgkin lymphoma (cHL)¹

KEYTRUDA as monotherapy is indicated for the treatment of adult and paediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma who have failed autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT is not a treatment option.

Urothelial carcinoma¹

KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy.

KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy and whose tumours express PD-L1 with a combined positive score (CPS) ≥ 10.

Head and neck squamous cell carcinoma (HNSCC)¹

KEYTRUDA, as monotherapy or 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 in adults whose tumours express PD-L1 with a CPS ≥ 1.

KEYTRUDA as monotherapy is indicated for the treatment of recurrent or metastatic head and neck squamous cell carcinoma in adults whose tumours express PD-L1 with a ≥ 50% TPS and progressing on or after platinum-containing chemotherapy.

Renal cell carcinoma (RCC)¹

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of advanced renal cell carcinoma in adults.

Colorectal cancer (CRC)¹

KEYTRUDA as monotherapy is indicated for the first-line treatment of metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer in adults.

Oesophageal carcinoma¹

KEYTRUDA, in combination with platinum and fluoropyrimidine based chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic carcinoma of the oesophagus or HER-2 negative gastroesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥ 10.

KEYTRUDA is a humanised monoclonal antibody which binds to the programmed cell death-1 (PD-1) receptor and blocks its interaction with ligands PD-L1 and PD-L2. The PD-1 receptor is a negative regulator of T-cell activity that has been shown to be involved in the control of T-cell immune responses. KEYTRUDA potentiates T-cell responses, including anti-tumour responses, through blockade of PD-1 binding to PD-L1 and PD-L2, which are expressed in antigen presenting cells and may be expressed by tumours or other cells in the tumour microenvironment.

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.

The recommended dose of KEYTRUDA as monotherapy in paediatric patients aged 3 years and older with cHL is 2 mg/kg bodyweight  (bw)(up to a maximum of 200 mg), every 3 weeks administered as an intravenous infusion over 30 minutes.

Patients should be treated with KEYTRUDA until disease progression or unacceptable toxicity. Atypical responses (i.e. an initial transient increase in tumour size or small new lesions within the first few months followed by tumour shrinkage) have been observed.

It is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed.

For the adjuvant treatment of melanoma, KEYTRUDA should be administered until disease recurrence, unacceptable toxicity, or for a duration of up to one year.

No dose reductions of KEYTRUDA are recommended. KEYTRUDA should be withheld or discontinued to manage adverse reactions.

The effects of various covariates on the pharmacokinetics of pembrolizumab were assessed in population pharmacokinetic analyses. The following factors had no clinically important effect on the clearance of pembrolizumab: age (range 15-94 years), gender, race, mild or moderate renal impairment, mild hepatic impairment and tumour burden. The relationship between body weight and clearance supports the use of either fixed dose or body weight-based dosing to provide adequate and similar control of exposure. Pembrolizumab exposure with weight-based dosing at 2 mg/kg every 3 weeks in paediatric patients (> 3 to 17 years) are comparable to those of adults at the same dose.

KEYTRUDA is not a chemotherapy and therefore chemotherapy handling precautions are not required.¹ Guidance on aseptic reconstitution can be found in the KEYTRUDA Product Information (see link in Reference section)

Severe infusion-related reactions, including hypersensitivity and anaphylaxis, have been reported in patients receiving pembrolizumab. For Grades 3 or 4 infusion reactions, infusion should be stopped and pembrolizumab permanently discontinued. Patients with Grades 1 or 2 infusion reaction may continue to receive pembrolizumab with close monitoring; premedication with antipyretic and antihistamine may be considered.

Corticosteroids can also be used as premedication, when pembrolizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions.

Refer to the KEYTRUDA Product Information for guidance on the management of mild or moderate, and severe infusion-related reactions.

Store in a refrigerator (2°C – 8°C). Do not freeze. For storage conditions after reconstitution or dilution of the medicinal product, see section 6.3 of Keytruda SPC.

Patients should be monitored for renal, hepatic functions and for endocrinopathies such as diabetes mellitus, hypophysitis and hypo or hyperthyroidism.

No formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab. Since pembrolizumab is cleared from the circulation through catabolism, no metabolic drug-drug interactions are expected.

The use of systemic corticosteroids or immunosuppressants before starting pembrolizumab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of pembrolizumab.

However, systemic corticosteroids or other immunosuppressants can be used after starting pembrolizumab to treat immune-related adverse reaction. Corticosteroids can also be used as premedication, when pembrolizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions.

Pembrolizumab is most commonly associated with immune-related adverse reactions. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of pembrolizumab.

The safety of pembrolizumab as monotherapy has been evaluated in 6,185 patients with advanced melanoma, resected Stage III melanoma (adjuvant therapy), NSCLC, cHL, urothelial carcinoma, HNSCC, or CRC across four doses (2 mg/kg every 3 weeks, 200 mg every 3 weeks, or 10 mg/kg every 2 or 3 weeks) in clinical studies. The frequencies included below are based on all reported adverse drug reactions, regardless of the investigator assessment of causality. In this patient population, the median observation time was 7.6 months (range: 1 day to 47 months) and the most frequent adverse reactions with pembrolizumab were fatigue (32%), nausea (21%), and diarrhoea (21%). The majority of adverse reactions reported for monotherapy were of Grades 1 or 2 severity. The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions.

The safety of pembrolizumab in combination with chemotherapy has been evaluated in 1,437 patients with NSCLC, HNSCC, or oesophageal carcinoma receiving 200 mg, 2 mg/kg bw or 10 mg/kg bw pembrolizumab every 3 weeks, in clinical studies. The frequencies included below are based on all reported adverse drug reactions, regardless of the investigator assessment of causality. In this patient population, the most frequent adverse reactions were nausea (55%), anaemia (51%), fatigue (39%), constipation (37%), decreased appetite (34%), diarrhoea (33%), neutropenia (29%),  and   vomiting (28%). Incidences of Grades 3-  5 adverse reactions in patients with NSCLC were 67% for pembrolizumab combination therapy and 66% for chemotherapy alone, in patients with HNSCC were 85% for pembrolizumab combination therapy and 84% for chemotherapy plus cetuximab, and in patients with oesophageal carcinoma were 86% for pembrolizumab combination therapy and 83% for chemotherapy alone.

The safety of pembrolizumab in combination with axitinib has been evaluated in a clinical study of 429 patients with advanced RCC receiving 200 mg pembrolizumab every 3 weeks and 5 mg axitinib twice daily. In this patient population, the most frequent adverse reactions were diarrhoea (54%), hypertension (45%), fatigue (38%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysaesthesia syndrome (28%), nausea (28%), ALT increased (27%), AST increased (26%), dysphonia (25%), cough (21%), and constipation (21%). Incidences of Grades 3-5 adverse reactions were 76% for pembrolizumab combination therapy and 71% for sunitinib alone.

1. Keytruda (pembrolizumab) Summary of Product characteristics (SPC). 25mg/ml concentrate for infusion. Last Accessed October 2021 
   https://www.medicines.ie/medicines/keytruda-25-mg-ml-concentrate-for-solution-for-infusion-32596