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
• Cutaneous squamous cell carcinoma
• Endometrial cancer
• Gastric cancer
• Head and neck squamous cell carcinoma
• Hepatocellular carcinoma
• Hodgkin lymphoma
• Melanoma
• Merkel cell carcinoma
• MSI-H or dMMR solid tumors (tissue-agnostic)
• Non-small cell lung cancer
• Primary mediastinal B-cell lymphoma
• Renal cell carcinoma
• Small cell lung cancer
• TMB-H solid tumors (tissue-agnostic)
• Triple-negative breast cancer (TNBC)

Patient drug information

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

Management checklist

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

History of changes in FDA indication

Dosing

• 4/28/2020: FDA accelerated approval to a new

"dosage of 400 mg every 6 weeks for all approved adult indications."

Bladder cancer

• 5/18/2017: 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. (New disease indication)
• 5/18/2017: Accelerated approval for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.
• 6/19/2018: Label revised for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing therapy and whose tumors express PD-L1 (Combined Positive Score ≥ 10), or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.
• 1/8/2020: FDA approved "for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy."

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

• 5/23/2017: Granted FDA accelerated approval for adult and pediatric patients with MSI-H or dMMR colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. (New disease indication)
• 6/29/2020: Approved for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. (Converted to regular approval; expanded to first-line setting)

Cutaneous squamous cell carcinoma

• 6/24/2020: Approved for patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation. (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)

• 3/14/2017: Accelerated 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. (New disease indication)
• 10/15/2020: FDA extended approval for the treatment of: "adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL) and pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy." (Approval extended to third-line setting)

Head and neck squamous cell carcinoma

• 8/5/2016: 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. (New disease indication)
• 6/10/2019: Approved for the first-line treatment of patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) in combination with platinum and fluorouracil (FU) for all patients and as a single agent for patients whose tumors express PD‑L1 (Combined Positive Score [CPS] ≥1) (Approval extended to first-line setting)

Hepatocellular carcinoma

• 11/9/2018: Accelerated approval for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. (New disease indication)

Melanoma

• 9/4/2014: Initial accelerated FDA approval for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab
  • 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

• 12/19/2018: Approved for adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). (New disease indication)

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. (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 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 [Biomarkers#alteration|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

• 6/13/2018: FDA approval expanded for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after two or more prior lines of therapy. (New disease indication)

Renal cell carcinoma

• 4/19/2019: Approved to be used together with axitinib for the first-line treatment of patients with advanced renal cell carcinoma (RCC). (New disease indication)

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)

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)

Also known as

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