Pembrolizumab

Pembrolizumab (KEYTRUDA)

🔴 Red Flag (Important) Information

• Immune-mediated adverse reactions can affect any organ system (lungs, liver, bowel, endocrine glands, kidneys, skin, heart) and may be life-threatening or fatal.

• Early recognition and prompt corticosteroid treatment are critical — delayed treatment increases morbidity and mortality.

• Permanently discontinue for severe or recurrent Grade 3–4 immune-mediated toxicity.

• Do not use in active autoimmune disease requiring systemic immunosuppression unless benefits clearly outweigh risks.

• Immune-mediated pneumonitis and colitis are among the most common serious toxicities.

• Endocrinopathies may be irreversible and require lifelong hormone replacement.

• Not interchangeable with chemotherapy toxicity profiles — normal labs do not exclude severe immune toxicity.

🔹 1. Basic Information

Generic name: Pembrolizumab
Brand name: KEYTRUDA
Drug class: Anti–PD-1 monoclonal antibody (immune checkpoint inhibitor)
Formulation: Concentrate for solution for IV infusion
Strengths: 100 mg/4 mL vial

Mechanism of Action:
Blocks the PD-1 receptor on T-cells → prevents interaction with PD-L1/PD-L2 → restores anti-tumour T-cell immune response.

🔹 2. Indications (SAHPRA-Approved – PI ONLY)

Melanoma

• Unresectable or metastatic melanoma

• Adjuvant treatment following complete resection of melanoma with lymph node involvement

Non-Small Cell Lung Cancer (NSCLC)

• First-line monotherapy for metastatic NSCLC with PD-L1 TPS ≥ 50%, without EGFR or ALK genomic tumour aberrations

• First-line combination therapy with platinum-based chemotherapy for metastatic NSCLC, regardless of PD-L1 expression

• Previously treated metastatic NSCLC after platinum-containing chemotherapy

Small Cell Lung Cancer (SCLC)

• Metastatic SCLC with disease progression after platinum-based chemotherapy and at least one other prior line of therapy

Head and Neck Squamous Cell Carcinoma (HNSCC)

• Recurrent or metastatic HNSCC:

  • As monotherapy for tumours expressing PD-L1 (CPS ≥ 1)

  • Or in combination with platinum and 5-fluorouracil as first-line treatment

Classical Hodgkin Lymphoma (cHL)

• Relapsed or refractory classical Hodgkin lymphoma

  • After failure of autologous stem cell transplant, or

  • In patients ineligible for transplant

Urothelial Carcinoma

• Locally advanced or metastatic urothelial carcinoma:

  • After platinum-containing chemotherapy, or

  • In cisplatin-ineligible patients whose tumours express PD-L1

Colorectal Cancer

• Unresectable or metastatic colorectal cancer

  • Tumours must be MSI-H or dMMR

  • After prior treatment

Gastric and Gastro-oesophageal Junction (GOJ) Cancer

• Recurrent or metastatic gastric or GOJ adenocarcinoma

  • Tumours expressing PD-L1 (CPS ≥ 1)

  • After two or more prior lines of therapy

Cervical Cancer

• Recurrent or metastatic cervical cancer

  • Tumours expressing PD-L1 (CPS ≥ 1)

  • After chemotherapy

Hepatocellular Carcinoma (HCC)

• Previously treated unresectable or metastatic HCC

  • After prior sorafenib therapy

Renal Cell Carcinoma (RCC)

• Advanced or metastatic renal cell carcinoma

  • In combination with axitinib as first-line therapy

Oesophageal Cancer

• Advanced or metastatic oesophageal carcinoma

  • Tumours expressing PD-L1

  • After prior chemotherapy

🔹 3. Dosing & Administration

• 200 mg IV every 3 weeks
  OR

• 400 mg IV every 6 weeks

Administration:

• IV infusion over 30 minutes

• No premedication routinely required

• Continue until disease progression or unacceptable toxicity

🔹 4. Dose Modifications

• No dose reductions

• Treatment interruption or permanent discontinuation based on toxicity severity

🔹 5. Contraindications

• Hypersensitivity to pembrolizumab or excipients

🔹 6. Monitoring Requirements

Baseline and ongoing:

• Clinical assessment for immune toxicity (every visit)

• Liver function tests

• Renal function

• Thyroid function (TSH ± free T4)

• Blood glucose

• Cortisol if clinically indicated

• Chest imaging if respiratory symptoms

🔹 7. Common Side Effects

Very Common / Common

• Fatigue

• Rash, pruritus

• Diarrhoea

• Nausea

• Arthralgia

• Decreased appetite

• Cough

Serious Immune-Mediated

• Pneumonitis

• Colitis

• Hepatitis

• Hypophysitis, thyroid dysfunction, adrenal insufficiency

• Nephritis

• Myocarditis

• Severe skin reactions

🔹 8. Use in Special Populations

• Pregnancy: Contraindicated

• Breastfeeding: Avoid

• Paediatrics: Limited indications only (as per PI)

• Autoimmune disease / transplant: Use with extreme caution

🔹 9. Duration of Use / When to Stop

Continue until:

• Disease progression, or

• Unacceptable toxicity

• (Usually otherwise stopped at 35 cycles - due to no data showing further use of drug) 

Permanently discontinue if:

• Life-threatening immune-mediated toxicity

• Recurrent Grade 3 toxicity

• Grade 4 immune-mediated adverse events (except controlled endocrinopathies)