Pembrolizumab — Drug Monograph
Brand names: Keytruda
Drug class: Checkpoint Inhibitor
Mechanism of Action
Humanized anti-PD-1 IgG4κ monoclonal antibody. Binds PD-1 on T cells, blocking interaction with PD-L1 and PD-L2 on tumor cells and antigen-presenting cells. Prevents inhibitory signaling, restoring T-cell antitumor activity. The most broadly approved checkpoint inhibitor, covering >30 tumor types including the first tumor-agnostic approvals (MSI-H/dMMR and TMB-H).
FDA Indications
- Melanoma — unresectable/metastatic; adjuvant (stages IIB, IIC, III, IV)
- NSCLC — first-line (PD-L1 ≥50%); first-line with chemotherapy (non-squamous and squamous)
- HNSCC — first-line (PD-L1 CPS ≥1); second-line after platinum failure
- Classical Hodgkin lymphoma (cHL) — after ≥3 prior therapies
- PMBCL — after ≥2 prior therapies
- Urothelial carcinoma — first-line (cisplatin-ineligible, PD-L1 CPS ≥10); second-line
- MSI-H/dMMR solid tumors — any histology (tumor-agnostic)
- TMB-H (≥10 mut/Mb) solid tumors — second-line (tumor-agnostic)
- Gastric/GEJ adenocarcinoma — HER2-negative, PD-L1 CPS ≥1, first-line with chemotherapy
- Esophageal cancer — first-line with platinum/fluoropyrimidine
- Cervical cancer — first-line (PD-L1 CPS ≥1) with chemo ± bevacizumab
- Hepatocellular carcinoma — after sorafenib
- Merkel cell carcinoma
- RCC — first-line with axitinib (Keynote-426)
- Endometrial carcinoma — dMMR; with lenvatinib (TMB unselected)
- TNBC — high-risk early (with chemo); metastatic PD-L1 CPS ≥10 (with chemo)
- Metastatic TNBC — first-line, in combination with sacituzumab govitecan for PD-L1-positive patients (ASCENT-04; June 24, 2026)
- Biliary tract cancer — first-line with gemcitabine/cisplatin
- Colorectal cancer (MSI-H/dMMR) — first-line
- NSCLC resectable — neoadjuvant/adjuvant with chemotherapy
- Muscle-invasive bladder cancer (MIBC) — perioperative (neoadjuvant + adjuvant) with enfortumab vedotin, all patients regardless of cisplatin eligibility (EV-304; July 10, 2026)
Common Side Effects
- Fatigue
- Musculoskeletal pain
- Rash (pruritus, vitiligo)
- Diarrhea
- Decreased appetite
- Nausea
- Hypothyroidism (very common with prolonged use)
- Infusion reactions (uncommon)
Clinical Pearl
Pembrolizumab has the broadest indication of any single oncology drug — >30 tumor types including tumor-agnostic MSI-H/dMMR (any solid tumor). Thyroid dysfunction is the most common endocrine irAE — hypothyroidism with levothyroxine can continue on pembrolizumab without dose change. Myocarditis is rare but highly lethal — new chest pain or heart failure symptoms in a patient on pembrolizumab requires urgent troponin measurement and cardiology consultation, and myocarditis of any grade mandates…
Related Therapies & Mechanisms
- Nivolumab (Opdivo) — Checkpoint Inhibitor · HCC
- Carboplatin (Paraplatin) — Breast
- Cisplatin (Platinol) — NSCLC
- Doxorubicin (Adriamycin) — Breast