pembrolizumab

General

Genetic Implications: Genetic Implications

Pronunciation:
pem-broe-li-zoo-mab


Trade Name(s)

  • Keytruda

Ther. Class.
antineoplastics

Pharm. Class.
monoclonal antibodies

Indications

  • Unresectable or metastatic melanoma.
  • Genetic implication First-line treatment of metastatic non-small cell lung cancer (NSCLC) with tumors with high PD-L1 expression (tumor expression score [TPS] ≥50%) with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations (as monotherapy).
  • Genetic implicationMetastatic NSCLC expressing PD-L1 (TPS ≥1%) that has progressed on or after platinum-containing chemotherapy (as monotherapy). Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.
  • First-line treatment of metastatic non-squamous NSCLC (in combination with pemetrexed and carboplatin).
  • Recurrent or metastatic head and neck squamous cell carcinoma that has progressed on or after platinum-containing chemotherapy.
  • Refractory classical Hodgkin lymphoma (cHL) in patients who have relapsed after ≥3 prior lines of therapy.
  • Locally advanced or metastatic urothelial carcinoma in patients who are not eligible for cisplatin-containing chemotherapy.
  • Locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-containing chemotherapy or within 12 mo of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
  • Unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient solid tumors that have progressed following prior treatment and have no satisfactory alternative treatment options.
  • Unresectable or metastatic, MSI-H, or mismatch repair deficient colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
  • Genetic implication Recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma expressing PD-L1 that has progressed on or after ≥2 prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy.

Action

Programmed death (PD) receptor-1–blocking antibody (an IgG4 kappa immunoglobulin) that blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2 resulting in inhibition of T-cell proliferation and decreased cytokine production.

Therapeutic Effect(s):

Decreased spread of melanoma, NSCLC, head and neck cancer, cHL, urothelial carcinoma, MSI-H, and gastric tumors.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism and Excretion: Unknown.

Half-life: 26 days.

TIME/ACTION PROFILE (response)

ROUTEONSETPEAKDURATION
IVwithin 3 mounknownmay persist for >8.8 mo

Contraindication/Precautions

Contraindicated in:

  • OB: Pregnancy (may cause fetal harm);
  • Lactation: Discontinue pembrolizumab or discontinue breast feeding.

Use Cautiously in:

  • Moderate to severe hepatic impairment;
  • Solid organ transplant recipients (may ↑ risk of rejection)
  • Rep: Women of reproductive potential;
  • Pedi: Safety and effectiveness not established.

Adverse Reactions/Side Effects

CNS: dizziness, fatigue, headache, insomnia

EENT: immune-mediated optic neuritis

Resp: IMMUNE-MEDIATED PNEUMONITIS

GI: IMMUNE-MEDIATED COLITIS, IMMUNE-MEDIATED HEPATITIS, ↓ appetite, constipation, diarrhea, nausea

GU: IMMUNE-MEDIATED NEPHRITIS

Derm: BULLOUS PEMPHIGOID, EXFOLIATIVE DERMATITIS, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, pruritus, rash, immune-mediated dermatitis, vitiligo

Endo: IMMUNE-MEDIATED HYPOPHYSITIS, immune-mediated hypothyroidism, immune-mediated hyperthyroidism, immune-mediated type 1 diabetes

MS: IMMUNE-MEDIATED RHABDOMYOLYSIS, arthralgia, back pain, extremity pain, myalgia, immune-mediated myasthenic syndrome

Hemat: anemia

Misc: INFUSION-RELATED REACTIONS, SEPSIS

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None noted.

Route/Dosage

Melanoma

IV (Adults) 200 mg every 3 wk until disease progression or unacceptable toxicity.

NSCLC, Head and Neck Cancer, Urothelial Carcinoma, or Gastric Cancer

IV (Adults) 200 mg every 3 wk until disease progression, unacceptable toxicity, or up to 24 mo in patients without disease progression.

cHL or MSI-H Cancer

IV (Adults) 200 mg every 3 wk until disease progression, unacceptable toxicity, or up to 24 mo in patients without disease progression.

IV Children 2 mg/kg (max = 200 mg) every 3 wk until disease progression, unacceptable toxicity, or up to 24 mo in patients without disease progression.

Availability

Lyophilized powder for injection: 50 mg/vial

Solution for injection: 25 mg/mL

Assessment

  • Monitor for signs and symptoms of immune-mediated pneumonitis (shortness of breath, chest pain, new or worse cough) periodically during therapy. Evaluate with x-ray. Treat with corticosteroids for ≥Grade 2 pneumonitis. Withhold pembrolizumab and monitor symptoms for moderate (Grade 2) pneumonitis; resume therapy when recovery to Grade 0 to 1. Permanently discontinue for severe (Grade 3) or life-threatening (Grade 4) pneumonitis.
  • Monitor for signs and symptoms of colitis (diarrhea, abdominal pain, mucus or blood in stool, with or without fever). Treat with corticosteroids for ≥Grade 2 colitis. Withhold pembrolizumab and monitor symptoms for moderate (Grade 2) or severe (Grade 3) colitis; resume therapy when recovery to Grade 0 to 1. Permanently discontinue for life-threatening (Grade 4) colitis.
  • Assess for signs and symptoms of immune-mediated hepatitis (yellowing of skin or whites of eyes, unusual darkening of urine, unusual tiredness, pain in right upper stomach) before each dose. Treat with corticosteroids for ≥Grade 2. Withhold or discontinue pembrolizumab depending on severity of liver enzyme elevations. Resume therapy when recovery to Grade 0 to 1.
  • Monitor for signs and symptoms of infusion-related reactions (rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, fever). For severe (Grade 3) or life-threatening (Grade 4), stop infusion and permanently discontinue therapy.
  • Monitor for clinical signs and symptoms of hypophysitis (persistent or unusual headache, extreme weakness, dizziness or fainting, vision changes) during therapy. Treat with corticosteroids for ≥Grade 2 hypophysitis. Withhold pembrolizumab and monitor symptoms for moderate (Grade 2) hypophysitis; withhold or discontinue for severe (Grade 3), and resume therapy when recovery to Grade 0 to 1. Permanently discontinue for life-threatening (Grade 4) hypophysitis.
  • Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome or toxic epidermal necrolysis. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.

Lab Test Considerations:

Monitor for changes in renal function. Treat with corticosteroids for ≥Grade 2 nephritis. Withhold pembrolizumab and monitor symptoms for moderate (Grade 2) nephritis; resume therapy when recovery to Grade 0 to 1. Permanently discontinue for severe (Grade 3) or life-threatening (Grade 4) nephritis.

  • Monitor for changes in thyroid function at start of and periodically during therapy, and as indicated based on clinical evaluation. Administer corticosteroids for ≥Grade 3 hyperthyroidism, withhold pembrolizumab for severe (Grade 3) hyperthyroidism and resume therapy when recovery to Grade 0 to 1. Permanently discontinue for life-threatening (Grade 4) hyperthyroidism. Manage hypothyroidism with thyroid replacement without interruption of therapy or corticosteroids.
  • Monitor serum blood glucose. May cause hyperglycemia or other signs and symptoms of diabetes.

Potential Diagnoses

Implementation

IV Administration

  • Intermittent Infusion: Reconstitute by injecting 2.3 mL of sterile water for injection along vial walls; swirl slowly, do not shake. Allow up to 5 min for bubbles to clear. Solution is clear to slightly opalescent, colorless to slightly yellow; do not administer solution if discolored or contains particulate matter other than translucent to white proteinaceous particles. Solution is stable at room temperature for up to 4 hr and 24 hr if refrigerated. Diluent: 0.9% NaCl. Mix using gently inversion.Concentration: 1 mg/mL to 10 mg/mL.
  • Rate:Infuse through a sterile, non-pyrogenic, low-protein binding 0.2 micron to 0.5 micron in-line or add-on filter over 30 min.
  • Y-Site Incompatibility: Do not administer other drugs through same infusion line.

Patient/Family Teaching

  • Explain purpose of pembrolizumab to patient.
  • Advise patient to notify health care professional immediately if signs and symptoms of pneumonitis, colitis, hepatitis, kidney problems (change in amount or color of urine), hormone gland problems (rapid heart beat, weight loss, increased sweating, weight gain, hair loss, feeling cold, constipation, deepening of voice, muscle aches, dizziness or fainting, persistent or unusual headache) occur.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Rep: Advise female patient of reproductive potential to use highly effective contraception during and for ≥4 mo after last dose; may cause fetal harm. Avoid breast feeding during therapy.
  • Emphasize importance of keeping scheduled appointments for blood work or other laboratory tests.

Evaluation/Desired Outcomes

Decreased spread of melanoma, NSCLC, head and neck cancer, cHL, urothelial carcinoma, MSI-H, and gastric tumors.

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