Keytruda is immunotherapy, not chemotherapy. The two treatments work in fundamentally different ways: chemotherapy uses drugs that are toxic to rapidly dividing cells, while Keytruda activates your own immune system to find and destroy cancer cells. That said, Keytruda is frequently prescribed alongside chemotherapy, which is likely why many people wonder about the distinction.
How Keytruda Works
Keytruda (pembrolizumab) belongs to a class of drugs called checkpoint inhibitors. To understand what that means, it helps to know that cancer cells often carry a protein on their surface that acts like an “off switch” for your immune system. When this protein connects with a receptor called PD-1 on your T cells (the immune cells responsible for attacking threats), it tells those T cells to stand down. The cancer essentially hides in plain sight.
Keytruda blocks PD-1, removing that disguise. With the off switch disabled, your T cells can recognize and attack the cancer. This is why immunotherapy side effects look so different from chemotherapy side effects: the drug isn’t poisoning fast-growing cells. It’s releasing the brakes on your immune system.
How This Differs From Chemotherapy
Chemotherapy drugs interfere with DNA replication or cell metabolism, killing cells that divide quickly. That includes cancer cells, but also healthy cells in your hair follicles, gut lining, and bone marrow, which is why chemo commonly causes hair loss, nausea, and a weakened immune system. Chemotherapy attacks the tumor directly.
Keytruda never touches the tumor itself. It works entirely through your immune system, which then does the attacking. This indirect approach means the treatment can sometimes produce durable, long-lasting responses. In a study of melanoma patients who achieved a complete response on checkpoint inhibitors like Keytruda, melanoma-specific survival was 96% at a median follow-up of about five years.
Why Keytruda Is Often Paired With Chemo
Even though Keytruda is not chemotherapy, your oncologist may prescribe it together with chemotherapy drugs. This combination is now standard first-line treatment for several cancers. The logic is straightforward: chemotherapy kills cancer cells quickly and can also release proteins from dying tumor cells that make it easier for the immune system to identify what to attack. Keytruda then keeps the immune response going over the long term.
FDA-approved combination regimens include Keytruda plus chemotherapy for:
- Non-small cell lung cancer (both squamous and nonsquamous types)
- Triple-negative breast cancer
- Head and neck squamous cell cancer
- Cervical cancer
- Gastric and esophageal cancers
- Pleural mesothelioma
- Endometrial cancer
- Biliary tract cancer
In these regimens, the chemotherapy portion typically lasts a set number of cycles (often four to six), while Keytruda continues on its own for up to about two years.
Who Is Eligible for Keytruda
Not every cancer responds to checkpoint inhibitors. Before prescribing Keytruda, your oncologist will usually test your tumor for specific biomarkers that predict whether the drug is likely to work.
The most common test measures PD-L1 expression, which tells doctors how much of the “off switch” protein your tumor produces. The result is reported as a Combined Positive Score (CPS). Different cancers have different CPS cutoffs for eligibility. For cervical cancer, for example, the threshold is a CPS of 1 or higher. For metastatic triple-negative breast cancer, the bar is set higher at CPS 10 or above.
A second biomarker is called microsatellite instability-high (MSI-H), sometimes described as mismatch repair deficiency. This refers to tumors with a high rate of DNA mutations caused by faulty repair mechanisms. These mutation-heavy tumors tend to produce more abnormal proteins that the immune system can target, making checkpoint inhibitors particularly effective. Keytruda was the first cancer drug ever approved based on a biomarker rather than the organ where the cancer started, meaning it can be used for MSI-H tumors regardless of where they occur in the body.
What Treatment Looks Like
Keytruda is given as an intravenous infusion, typically over about 30 minutes. Two dosing schedules are approved for adults: every three weeks or every six weeks, with the less frequent schedule approved in 2020 for greater convenience. A subcutaneous injection form was also approved in 2025 for patients 12 and older with solid tumors, which can be administered more quickly.
Treatment usually continues for up to two years, or 35 cycles at the three-week interval, as long as the cancer responds and side effects remain manageable. Some patients achieve a complete response before reaching that limit and stop treatment early.
Side Effects Compared to Chemotherapy
Because Keytruda revs up the immune system rather than poisoning cells, its side effect profile is distinctly different from chemotherapy. You generally won’t experience the classic chemo side effects like severe nausea, hair loss, or dramatically low blood counts. Instead, the risks center on your immune system attacking healthy tissues, a category called immune-related adverse events.
The most common of these include skin reactions like rash or itching, diarrhea (occurring in up to 19% of patients on the drug alone), and thyroid or other hormonal problems (roughly 10% of patients on checkpoint inhibitors develop clinically significant endocrine issues). Lung inflammation, or pneumonitis, occurs in about 2.7% of patients. Joint pain and arthritis-like symptoms are also relatively common and tend to occur more frequently with PD-1 inhibitors like Keytruda than with some other immunotherapy drugs.
Rarer but more serious immune-related side effects can affect the kidneys (1-2% for any severity), nervous system, or heart (less than 0.1%). When Keytruda is combined with chemotherapy, you can experience side effects from both treatments, which means the overall burden tends to be heavier than with either approach alone. Severe skin reactions occur in about 3% or fewer patients on Keytruda alone, and severe kidney injury in less than 1%.
The key practical difference is that most immune-related side effects from Keytruda are reversible when caught early. Your care team will monitor blood work and symptoms closely throughout treatment, and temporary pauses or dose adjustments are common if your immune system starts targeting healthy tissue.