What is Pembrolizumab (Keytruda)?
Pembrolizumab, widely known by its brand name Keytruda, is a revolutionary medication in the field of oncology [1.2.2]. Developed by Merck, it represents a significant advancement in cancer treatment, moving away from traditional cytotoxic methods towards harnessing the body's own immune system [1.4.3]. First approved by the FDA in 2014 for advanced melanoma, its applications have expanded dramatically, now covering a wide array of cancers [1.2.3, 1.5.2]. It is administered as an intravenous (IV) infusion, typically over 30 minutes, with a schedule of once every 3 or 6 weeks depending on the cancer type and treatment plan [1.7.1, 1.7.2]. Recently, in September 2025, a subcutaneous (under the skin) injection form called Keytruda Qlex was also approved for many of the same indications [1.4.1, 1.4.3].
The Core Question: What class of drug is pembrolizumab?
Pembrolizumab belongs to a class of drugs called immune checkpoint inhibitors [1.2.2]. More specifically, it is a humanized monoclonal antibody that targets the Programmed Death 1 (PD-1) receptor [1.2.3, 1.3.3]. This dual classification is key to understanding its function.
- Monoclonal Antibody: These are lab-created proteins designed to mimic the natural antibodies produced by the immune system [1.2.2]. They are engineered to target a specific protein, in this case, the PD-1 receptor on T-cells [1.2.4, 1.3.3].
- Immune Checkpoint Inhibitor: The immune system has 'checkpoints,' which are molecules on certain immune cells that need to be activated or inactivated to start an immune response. Cancer cells can sometimes exploit these checkpoints to avoid being attacked by the immune system. Pembrolizumab blocks one such checkpoint, releasing the 'brakes' on the immune response [1.2.2, 1.3.1].
The Mechanism of Action: How PD-1 Inhibitors Work
The primary function of pembrolizumab is to block the interaction between the PD-1 receptor on T-cells (a type of immune cell) and its ligands, PD-L1 and PD-L2, which are often found on the surface of cancer cells [1.3.1, 1.3.2]. When PD-L1 or PD-L2 bind to PD-1, it sends an 'off' signal to the T-cell, preventing it from attacking the cancer cell [1.3.2].
Pembrolizumab works by binding directly to the PD-1 receptor. This action physically prevents the PD-L1 and PD-L2 ligands from docking with the T-cell [1.3.1]. By blocking this inhibitory signal, pembrolizumab effectively 'unmasks' the cancer cells, allowing the T-cells to recognize them as invaders and mount a robust attack, thereby slowing or stopping tumor growth [1.2.1, 1.3.2].
Approved Uses for Pembrolizumab
Pembrolizumab is FDA-approved to treat a multitude of cancers, often when the disease is advanced, has spread, or has not responded to other treatments [1.2.3]. The list of indications is extensive and continues to grow, including but not limited to:
- Melanoma (skin cancer) [1.5.2]
- Non-Small Cell Lung Cancer (NSCLC) [1.5.2]
- Head and Neck Squamous Cell Carcinoma (HNSCC) [1.5.3]
- Classical Hodgkin Lymphoma (cHL) [1.5.3]
- Urothelial Carcinoma (bladder cancer) [1.5.3]
- Endometrial Carcinoma [1.5.3]
- Cervical Cancer [1.5.3]
- Triple-Negative Breast Cancer (TNBC) [1.5.2]
- Renal Cell Carcinoma (kidney cancer) [1.5.2]
- Hepatocellular Carcinoma (liver cancer) [1.5.2]
- Solid tumors with specific genetic features like microsatellite instability-high (MSI-H) [1.5.3]
Understanding Immune-Related Adverse Events
Because pembrolizumab works by activating the immune system, its side effects are primarily immune-related. These occur when the stimulated immune system begins to attack healthy tissues and organs [1.13.1]. While many side effects are manageable, some can be severe or life-threatening [1.6.2, 1.13.3]. Common immune-related adverse events (irAEs) can affect various systems:
- Skin: Rash, itching (pruritus), and severe reactions like Stevens-Johnson syndrome [1.6.1, 1.13.1].
- Gastrointestinal: Diarrhea and colitis (inflammation of the colon) [1.13.2].
- Lungs: Pneumonitis (inflammation of the lungs) [1.13.1].
- Endocrine Glands: Hypothyroidism, hyperthyroidism, and adrenal insufficiency [1.13.2].
- Liver: Hepatitis (inflammation of the liver) [1.13.1].
- Kidneys: Nephritis (inflammation of the kidneys) [1.13.2].
Close monitoring by a healthcare team is crucial to identify and manage these potential toxicities promptly [1.13.2].
Comparison Table: Pembrolizumab vs. Other Treatments
| Feature | Pembrolizumab (Keytruda) | Traditional Chemotherapy | Nivolumab (Opdivo) |
|---|---|---|---|
| Mechanism | Immune Checkpoint Inhibitor (PD-1); boosts immune response against cancer [1.3.1]. | Directly kills rapidly dividing cells (both cancerous and healthy) [1.8.2]. | Immune Checkpoint Inhibitor (PD-1); boosts immune response against cancer [1.9.1]. |
| Target | Specific: PD-1 protein on T-cells [1.3.3]. | Non-specific: any rapidly dividing cell [1.8.2]. | Specific: PD-1 protein on T-cells [1.9.3]. |
| Administration | IV infusion or subcutaneous injection, every 3-6 weeks [1.4.3, 1.7.1]. | Often more frequent cycles (e.g., weekly or every few weeks) [1.8.2]. | IV infusion; dosing schedules vary [1.9.1]. |
| Common Side Effects | Fatigue, rash, diarrhea, immune-related inflammation (colitis, pneumonitis) [1.7.1, 1.13.2]. | Nausea, hair loss, fatigue, low blood counts (cytopenias) [1.8.2]. | Similar to Pembrolizumab; fatigue, rash, diarrhea, immune-related side effects [1.9.1]. |
| Key Difference | Has a wider range of FDA-approved indications compared to Nivolumab [1.9.1]. | Attacks cells directly, leading to different toxicity profile [1.8.2]. | Approved for use with other immunotherapies like ipilimumab; dosing and indications differ slightly from Pembrolizumab [1.9.1]. |
The Future of PD-1 Inhibition
The field of immuno-oncology is rapidly evolving. The market for PD-1/PD-L1 inhibitors is projected to grow significantly, driven by rising cancer incidence and expanding clinical applications [1.12.1]. Future research is focused on several key areas:
- Combination Therapies: Exploring pembrolizumab in combination with other immunotherapies, targeted therapies, and chemotherapy to improve outcomes [1.12.1, 1.8.1].
- Biomarkers: Identifying better biomarkers beyond PD-L1 expression to predict which patients are most likely to respond to treatment [1.10.3].
- New Formulations: Developing novel delivery methods, such as small-molecule inhibitors that could potentially be taken orally, offering advantages in administration and cost [1.12.3].
- AI in Drug Discovery: Utilizing artificial intelligence to accelerate the discovery of new drugs and optimize clinical trial design [1.12.1].
Conclusion
Pembrolizumab is firmly established as a cornerstone of modern cancer therapy. It is classified as an immune checkpoint inhibitor and a monoclonal antibody that works by blocking the PD-1 pathway, thereby enabling the immune system to fight cancer [1.2.2, 1.2.4]. Its proven efficacy across a growing list of malignancies has fundamentally changed the treatment landscape [1.4.2]. While it offers the potential for durable, long-term responses and a different side effect profile than traditional chemotherapy, it requires careful management of unique immune-related adverse events [1.8.2, 1.13.3]. As research continues, the role of pembrolizumab and other PD-1 inhibitors in oncology is set to expand even further.
Authoritative Link: National Cancer Institute - Pembrolizumab
