Pembrolizumab (Keytruda)

Indications for Programmed Cell Death 1 (PD-1) Checkpoint Inhibitors

  • Castration-Resistant Prostate Cancer (see Prostate Cancer, [[Prostate Cancer]])
  • Colorectal Cancer (see Colorectal Cancer, [[Colorectal Cancer]])
  • Melanoma (see Melanoma, [[Melanoma]])
    • Pembrolizumab (Keytruda) Has Been FDA Approved (see Pembrolizumab, [[Pembrolizumab]])
  • Non-Small Cell Lung Cancer with Progression On/After Platinum-Based Chemotherapy (see Lung Cancer, [[Lung Cancer]])
    • Nivolumab Has Been FDA-approved for Both Squamous and Non-Squamous Non-Small Cell Lung Cancers
  • Renal Cell Carcinoma (see Renal Cancer, [[Renal Cancer]])

Pharmacology

  • Programmed Cell Death 1 (PD-1) Checkpoint Inhibitor (see PD-1 Checkpoint Inhibitors, [[PD-1 Checkpoint Inhibitors]]): PD-1 is a key immune-checkpoint receptor expressed by activated T cells -> it mediates immunosuppression
    • T-Cells Encounter the Immunosuppressive PD-1 Ligands, PD-L1 (B7-H1) and PD- L2 (B7-DC), Which are Expressed by Tumor Cells and/or Stromal Cells
    • Pembrolizumab is a Monoclonal Antibody Against PD-1: inhibition of the interaction between PD-1 and PD-L1 enhances T-cell responses in vitro and mediates anti-tumor activity

Metabolism

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Administration

  • xxxx

Dose Adjustment

  • Hepatic:
  • Renal:

Adverse Effects

Dermatologic Adverse Effects

  • Pruritus (see Pruritus, [[Pruritus]])
  • Rash
  • Vitiligo (see Vitiligo, [[Vitiligo]])

Endocrinologic Adverse Effects

  • Hypophysitis
  • Thyroiditis

Gastrointestinal/Hepatic Adverse Effects

Neurologic Adverse Effects

Pulmonary Adverse Effects

Pulmonary Toxicity

  • Epidemiology
    • Time of Onset: onset of pneumonitis occurs 7.4-24.3 months after the initiation of therapy
  • Physiology: immune-mediated toxic effect
  • Clinical Patterns
  • Treatment: corticosteroids (see Corticosteroids, [[Corticosteroids]])

Other Adverse Effects

  • Fever (see Fever, [[Fever]])

References

  • Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2 [MEDLINE]
  • Anti-PD-1-Related Pneumonitis during Cancer Immunotherapy. N Engl J Med. 2015 Jul 16;373(3):288-90. doi: 10.1056/NEJMc1505197 [MEDLINE]