Pembrolizumab (Keytruda)

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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.[1][2][3]
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.[1]

Diseases for which it is used

Patient drug information

Management checklist

  • CBC, comprehensive metabolic panel, Mg, Phos, LDH, TSH. Consider baseline EKG and troponin.

History of changes in FDA indication

Bladder cancer

Cervical cancer

  • 6/12/2018: Approved 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. (New disease indication)

Endometrial cancer

  • 9/17/2019: Accelerated approval in combination with Lenvatinib (Lenvima) for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation. (New disease indication)

Esophageal cancer

  • 7/30/2019: Approved for patients with recurrent, locally advanced or metastatic, squamous cell carcinoma of the esophagus (ESCC) whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10), as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy. (New disease indication)

Gastric or gastroesophageal junction adenocarcinoma

  • 9/22/2017: 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. (New disease indication)

Classical Hodgkin lymphoma (cHL)

Head and neck squamous cell carcinoma

Hepatocellular carcinoma

Melanoma

  • 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.
  • 12/18/2015: Label expanded for the treatment of patients with unresectable or metastatic melanoma. (Requirement for progression removed)
  • 2/15/2019: Approved for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection. (Indication expanded to adjuvant setting)

Merkel cell carcinoma

MSI-H or dMMR tumors (tissue-agnostic)

  • 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. (New disease-agnostic indication)

Non-small cell lung cancer

  • 10/2/2015: Accelerated 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. (New disease indication)
  • 10/24/2016: 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. (first-line indication with biomarker requirement)
    • 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.
  • 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). (first-line indication with histology requirement)
  • 8/20/2018: Granted regular approval in combination with pemetrexed and platinum as first-line treatment of patients with metastatic, non-squamous non-small cell lung cancer (NSqNSCLC), with no EGFR or ALK genomic tumor aberrations. (conversion to regular approval)
  • 10/30/2018: Approval expanded in combination with carboplatin and either paclitaxel or nab-paclitaxel as first-line treatment of metastatic squamous non-small cell lung cancer (NSCLC). (first-line indication with histology requirement)
  • 4/11/2019: Approval expanded for the first-line treatment of patients with stage III non-small cell lung cancer (NSCLC) who are not candidates for surgical resection or definitive chemoradiation or metastatic NSCLC. Patients’ tumors must have no EGFR or ALK genomic aberrations and express PD-L1 (Tumor Proportion Score [TPS] greater than or equal to 1%) (approval expanded to the non-metastatic setting)

Primary mediastinal B-cell lymphoma

Renal cell carcinoma

Small cell lung cancer

  • 6/17/2019: Accelerated approval for patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. (New disease indication)

Also known as

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

References