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

Diseases for which it was 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

Dosing

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)

Colorectal cancer

Cutaneous squamous cell carcinoma

Endometrial cancer

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)
  • 3/22/2021: Approved in combination with platinum and fluoropyrimidine-based chemotherapy for patients with metastatic or locally advanced esophageal or gastroesophageal (GEJ) (tumors with epicenter 1 to 5 centimeters above the gastroesophageal junction) carcinoma who are not candidates for surgical resection or definitive chemoradiation. (Histology-specific restriction removed; protein expression requirement removed; prior therapy requirement removed; surgery and radiation eligibility restriction added; drug combination requirement added)

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

Merkel cell carcinoma

MSI-H or dMMR tumors (tissue-agnostic)

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 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)
  • 10/24/2016: Label expanded for 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

TMB-H (tissue agnostic)

  • 6/16/2020: Accelerated approval for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. (New disease-agnostic indication)

Triple-negative breast cancer (TNBC)

  • 11/13/2020: Accelerated approval in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS ≥10) as determined by an FDA approved test. (New disease indication)

Withdrawn indications

Small cell lung cancer

Also known as

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

References