Drugs of interest to pathologists
Drugs related to surgical pathology

Topic Completed: 1 November 2017

Minor changes: 22 August 2019

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PubMed Search: Pembrolizumab[title] review[ptyp]

Him G. Kwee, M.D.
Page views in 2019: 485
Page views in 2020 to date: 265
Cite this page: Kwee HG. Pembrolizumab. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/drugspembrolizumab.html. Accessed August 8th, 2020.
Definition / general
  • Humanized antibody targeting the programmed death receptor 1 (PD-1) located on lymphocytes
  • By binding with PD-1, it blocks immune suppressing ligands PDL1 and PDL2 from interacting with PD-1, which restores T cell and other immune response to attack the tumor (Merck: Keytruda Product Insert [Accessed 14 December 2018])
Trade name
  • Keytruda®
  • Melanoma: unresectable or metastatic
  • Nonsmall cell lung carcinoma:
    • First line treatment as a single drug for advanced or metastatic disease with PDL1 tumor proportion score (TPS) of 50% or above, with no EGFR or ALK gene aberration
    • First line combination therapy with pemetrexed and carboplatin for disease with any level of tumor PDL1 expression or no PD-1 expression
    • Advanced or metastatic disease if not responding to second line platinum therapy, and have a PDL1 TPS of 1% or above and are not responding to EGFR or ALK inhibitors although they have EGFR or ALK gene aberrations
    • Advanced or metastatic nonsquamous lung carcinoma patients who have received pemetrexed and carboplatin as first treatment
  • Head and neck squamous cell carcinoma: recurrent or metastatic, refractory to chemotherapy that contains platinum
  • Classical Hodgkin lymphoma: refractory or relapsed, after receiving 3 or more types of treatment
  • Urothelial carcinoma: advanced or metastatic, refractory to platinum or unable to receive cisplatin
  • Microsatellite instability high (MSI-H) or MMR deficient solid tumors or colorectal carcinoma: unresectable or metastatic, refractory to fluoropyrimidine, oxaloplatin and irinotectan
  • Gastric or gastroesophageal junction adenocarcinoma: advanced or metastatic, testing positive for PDL1, who have received 2 or more chemotherapies including fluoropyrimidine and platinum and have abnormal HER2/neu gene but are refractory to HER2/neu targeted therapy
Use for pathologists
  • FDA has approved a companion test: PDL1 IHC 22C3 pharmDx (Dako, Carpinteria, CA), a monoclonal mouse anti-PDL1 antibody for the detection of PDL1 protein in FFPE tissue
  • Some laboratories use other antibodies and other platforms after performing comparison validation studies against this antibody and the Dako platform (Arch Pathol Lab Med 2016;140:341)
  • Minimum of 100 viable tumor cells is necessary for interpretation
  • Partial or complete membranous staining of tumor cells at any intensity is regarded as positive; cytoplasmic staining is nonspecific
  • Tumor proportion score (TPS) is the percentage of viable tumor cells staining positive; lymphocytes and macrophages should not be included in the count (Agilent: PD-L1 IHC 22C3 pharmDx [Accessed 14 December 2018])
  • Lung adenocarcinoma
    • Subtypes with the least frequent PDL1 expression are acinar, mucinous and papillary
    • Subtypes with the most frequent PDL1 expression are solid, micropapillary and lepidic
    • If the biopsy specimen is small, tumor staining is negative for PDL1 but the tumor shows either a solid or micropapillary or lepidic pattern, a second biopsy specimen may need to be obtained (Arch Pathol Lab Med 2017;141:1529)
Microscopic (histologic) images

Contributed by Andrey Bychkov, M.D., Ph.D.

Lung adenocarcinoma

Board review style question #1
A lung adenocarcinoma subtype with a less frequent PDL1 expression includes:

  1. Lepidic
  2. Micropapillary
  3. Papillary
  4. Solid
  5. None of the above
Board review answer #1
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