Pembrolizumab (Keytruda)

General information

Class/mechanism: PD-1 antibody. Pembrolizumab is a humanized monoclonal antibody which binds to the PD-1 receptor on T-cells. In some cancers, the PD-1 ligands are upregulated, which results in inhibition of T-cell immune surveillance of tumors. By blocking the interaction between the PD-1 receptor and its ligands PD-L1 and PD-L2, pembrolizumab decreases this immune system inhibition and facilitates anti-tumor immune response.
Route: IV
Extravasation: no information

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is used

• Bladder cancer
• Cervical cancer
• Colon cancer
• Gastric cancer
• Head and neck squamous cell carcinoma
• Hodgkin lymphoma
• Melanoma
• Merkel cell carcinoma
• MSI-H or dMMR tumors (tissue-agnostic)
• Non-small cell lung cancer

Patient drug information

• Pembrolizumab (Keytruda) patient drug information (Chemocare)
• Keytruda wallet card about side effects
• Pembrolizumab (Keytruda) patient drug information (UpToDate)
• Pembrolizumab (Keytruda) package insert

Management checklist

• CBC, comprehensive metabolic panel, Mg, Phos, LDH, TSH

History of changes in FDA indication

• 9/4/2014: Initial accelerated FDA approval "for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor."
• 10/2/2015: Accelerated FDA approval for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express programmed death ligand 1 (PD-L1) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.
• 12/18/2015: FDA label expanded "for the treatment of patients with unresectable or metastatic melanoma."
• 8/5/2016: FDA label expanded "for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy."
• 10/24/2016: FDA label expanded for the following indications:
  • "Patients with metastatic NSCLC whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] greater than or equal to 50%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC."
  • "Patients with metastatic NSCLC whose tumors express PD-L1 (TPS greater than or equal to 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab."
• 3/14/2017: Granted accelerated FDA approval "for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or those who have relapsed after three or more prior lines of therapy."
• 5/10/2017: FDA accelerated approval to be used "in combination with pemetrexed and carboplatin for the treatment of patients with previously untreated metastatic non-squamous non-small cell lung cancer (NSCLC)."
• 5/18/2017: FDA regular approval for "patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy."
• 5/18/2017: Granted FDA accelerated approval for "patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy."
• 5/23/2017: Granted FDA accelerated approval for "adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options or with MSI-H or dMMR colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan."
• 9/22/2017: Granted FDA accelerated approval "for patients with recurrent locally advanced or metastatic, gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 as determined by an FDA-approved test. Patients must have had disease progression on or after two or more prior systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy."
• 6/12/2018: FDA approval expanded "for patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test."

Also known as

• Code names: MK-3475, SCH 900475
• Generic names: lambrolizumab
• Brand name: Keytruda