Keytruda works by removing a “brake” that cancer puts on your immune system, freeing your body’s own T cells to recognize and attack tumor cells. It belongs to a class of drugs called immune checkpoint inhibitors, and it targets a specific protein on T cells called PD-1. Rather than killing cancer directly like chemotherapy does, Keytruda restores your immune system’s ability to do the job itself.
The PD-1 Brake System
Your immune system has built-in safety switches that prevent T cells from attacking healthy tissue. One of these switches is a protein on T cells called PD-1 (programmed cell death protein 1). When PD-1 connects with a matching protein called PD-L1 on another cell, it tells the T cell to stand down. Under normal circumstances, this is a good thing. It keeps your immune system from damaging your own organs.
Cancer cells exploit this system. Many tumors produce PD-L1 on their surface, essentially disguising themselves as normal tissue. When a T cell approaches the tumor and its PD-1 receptor locks onto the tumor’s PD-L1, the T cell receives a “stop” signal. It won’t activate, won’t multiply, and won’t release the chemicals that kill abnormal cells. The tumor grows unchecked while the immune system idles nearby.
How Keytruda Releases the Brake
Keytruda (pembrolizumab) is an antibody that binds directly to the PD-1 receptor on T cells. By physically occupying that receptor, it blocks PD-L1 on the tumor from connecting. Without that “stop” signal, T cells reactivate. They begin multiplying, recognizing the cancer as a threat, and attacking it. This discovery was significant enough that the researchers behind it, James Allison and Tasuku Honjo, won the 2018 Nobel Prize in Physiology or Medicine.
The key distinction from chemotherapy is specificity. Chemotherapy poisons rapidly dividing cells throughout the body, cancerous or not. Keytruda doesn’t touch the cancer directly. It simply restores immune function that the tumor had suppressed, which means the attack is more targeted. Your T cells can distinguish tumor cells from healthy ones in ways that chemotherapy cannot.
How Treatment Is Given
Keytruda is delivered as an intravenous infusion, typically over about 30 minutes. The standard schedule for adults is 200 mg every three weeks or 400 mg every six weeks. The FDA approved the six-week option in 2020 across all adult uses, giving patients fewer clinic visits with comparable results. Treatment duration varies by cancer type, but many patients receive Keytruda for up to two years if their cancer responds and side effects remain manageable.
Biomarker Testing and Eligibility
Not every cancer responds to Keytruda, and not every patient qualifies. In many cases, your oncologist will order a biopsy-based test to measure how much PD-L1 your tumor produces. The standard test is an assay called the 22C3 PharmDx, which scores PD-L1 levels using two methods: a Tumor Proportion Score (TPS) that looks only at cancer cells, and a Combined Positive Score (CPS) that also counts immune cells in the tumor environment.
For some cancers, like advanced lung cancer, higher PD-L1 expression generally means a stronger case for Keytruda. Patients with a TPS of 50% or above may receive Keytruda alone as a first-line treatment. Those with lower expression (TPS 1% to 49%) often receive Keytruda combined with chemotherapy. Even patients with no detectable PD-L1 expression can sometimes qualify for Keytruda-chemotherapy combinations, depending on the cancer type.
A separate biomarker called MSI-H or dMMR matters for certain solid tumors. These markers indicate that a cancer has trouble repairing its own DNA, which creates many mutations and makes the tumor more visible to the immune system. Keytruda is approved for MSI-H or dMMR tumors regardless of where in the body they originated, one of the first cancer approvals based on a genetic feature rather than tumor location.
Cancers Keytruda Treats
Keytruda has one of the broadest approval lists of any cancer drug. It is currently approved for more than 15 cancer types, including melanoma, non-small cell lung cancer, head and neck cancer, bladder and urinary tract cancers, Hodgkin lymphoma, cervical cancer, liver cancer, esophageal cancer, gastric cancer, biliary tract cancer, Merkel cell carcinoma, and mesothelioma. Some approvals cover advanced or metastatic disease, while others cover earlier-stage cancers before or after surgery.
In advanced melanoma, long-term data from the landmark KEYNOTE-001 trial showed three-year overall survival of 45% in patients receiving Keytruda as their first treatment. For context, median survival with chemotherapy alone in advanced melanoma was about 11 months, while Keytruda extended that to roughly 13 to 15 months depending on the dose studied. Real-world studies have found similar or better results: one analysis reported that about 35% of patients achieved a complete response, with progression-free survival exceeding 94% at three years after stopping treatment in those who responded.
In lung cancer, Keytruda is now a cornerstone of first-line treatment. The most recent clinical guidelines recommend it combined with platinum-based chemotherapy for most patients with advanced non-small cell lung cancer, regardless of PD-L1 levels. For patients with high PD-L1 expression who cannot tolerate or decline combination therapy, Keytruda alone remains an option.
Side Effects and Immune Reactions
Because Keytruda works by releasing the brakes on your immune system, the main risk is that your immune system overshoots and attacks healthy tissue. These are called immune-related adverse events, and they occur in roughly 40% of patients at some level. Most are mild to moderate: skin rashes, fatigue, diarrhea, or thyroid problems that cause your gland to become overactive or underactive.
About 20% of patients experience more serious immune reactions. The organs most commonly affected are the gut, skin, and endocrine glands like the thyroid and pituitary. Less common but more dangerous reactions involve the lungs (inflammation that causes shortness of breath), the heart, and the nervous system. The pattern of side effects can differ by cancer type. Patients with melanoma tend to experience more skin and gut reactions, while those with lung cancer may see more joint pain and skin inflammation.
Most immune-related side effects are reversible when caught early. Treatment typically involves pausing Keytruda and using steroids to calm the immune response. Some endocrine side effects, particularly thyroid dysfunction, can become permanent and require lifelong hormone replacement. Your care team will monitor bloodwork regularly throughout treatment to catch these reactions before they become severe.
Why It Works Better for Some Patients
Response to Keytruda varies widely. Some patients see dramatic, lasting tumor shrinkage, while others get little benefit. PD-L1 expression is part of the picture but not the whole story. Tumors with more genetic mutations tend to respond better because they produce more abnormal proteins for T cells to recognize. This is why MSI-H cancers, which accumulate mutations rapidly, respond particularly well.
The composition of the tumor environment matters too. A tumor that already has T cells infiltrating it but being held in check by PD-L1 is primed to respond when Keytruda removes that block. A tumor with very few immune cells nearby, sometimes called an immunologically “cold” tumor, often responds poorly because there simply aren’t enough T cells present to mount an attack, even with the brake removed. Ongoing work is focused on combining Keytruda with other treatments to convert cold tumors into hot ones, making more patients eligible for a meaningful response.