Keytruda (pembrolizumab) is the first immunotherapy approved for breast cancer, and its effectiveness depends heavily on the type and stage of disease. It is only approved for triple-negative breast cancer (TNBC), a subtype that accounts for roughly 10 to 15 percent of all breast cancers. In early-stage TNBC, adding Keytruda to chemotherapy increased the rate of complete tumor elimination from 51% to nearly 65%. In metastatic TNBC, it extended median survival by about seven months, but only in patients whose tumors met a specific biomarker threshold.
Why Keytruda Only Works in Triple-Negative Breast Cancer
Keytruda is an immune checkpoint inhibitor. It blocks a protein called PD-1 on immune cells, which cancer cells exploit to hide from the immune system. By blocking that protein, Keytruda essentially removes the brakes on your immune response, allowing T-cells to recognize and attack cancer cells.
Triple-negative breast cancer lacks the three receptors (estrogen, progesterone, and HER2) that other breast cancers use to grow, which means it can’t be treated with hormone therapy or HER2-targeted drugs. However, TNBC tumors tend to produce higher levels of the immune-evading protein PD-L1, making them more responsive to immunotherapy. Other breast cancer subtypes generally don’t produce enough PD-L1 for Keytruda to make a meaningful difference, which is why it has no FDA approval for those types.
Effectiveness in Early-Stage TNBC
For high-risk, early-stage TNBC, Keytruda is given alongside chemotherapy before surgery (neoadjuvant treatment) and then continued alone after surgery (adjuvant treatment). The landmark KEYNOTE-522 trial established the numbers that led to FDA approval.
In that trial, 64.8% of patients who received Keytruda plus chemotherapy had a pathological complete response, meaning no cancer was detectable in the tissue removed during surgery. In the chemotherapy-only group, that figure was 51.2%. That 13.6 percentage point difference was statistically significant. Notably, patients were enrolled regardless of their tumor’s PD-L1 levels, so this benefit applied broadly across the early-stage TNBC population.
The longer-term data is equally important. At five years, 81.2% of patients in the Keytruda group were free of cancer recurrence or death, compared to 72.2% in the chemotherapy-only group. That nine-point gap in event-free survival represents a 35% reduction in the risk of the cancer coming back or progressing. These results have established the Keytruda-plus-chemotherapy combination as the standard of care for high-risk early-stage TNBC.
Effectiveness in Metastatic TNBC
For locally recurrent or metastatic TNBC, where the cancer has spread or can’t be surgically removed, the picture is more nuanced. Keytruda is only approved for patients whose tumors have a PD-L1 Combined Positive Score (CPS) of 10 or higher, a measure of how much PD-L1 protein is present in and around the tumor. Your oncologist will order a specific lab test to determine this score before treatment.
In the KEYNOTE-355 trial, patients with CPS scores of 10 or higher who received Keytruda plus chemotherapy had a median overall survival of 23 months, compared to 16.1 months for chemotherapy alone. That’s nearly seven additional months of survival. For patients whose tumors had lower PD-L1 expression, the benefit was not significant enough to warrant approval, which is why the biomarker cutoff exists.
It’s worth putting this in context: metastatic TNBC has historically been one of the hardest cancers to treat, with limited options and short survival times. A seven-month improvement in median survival is meaningful for this disease, though it also underscores that Keytruda is not a cure for advanced TNBC. It extends life and, for some patients, can produce durable responses that last well beyond the median.
How Treatment Works in Practice
Keytruda is given as a 30-minute intravenous infusion, either 200 mg every three weeks or 400 mg every six weeks. In the early-stage setting, you’ll receive it alongside your chemotherapy regimen before surgery, then continue Keytruda alone afterward. For metastatic disease, it’s paired with chemotherapy on an ongoing basis.
The treatment cycle becomes a regular part of your schedule. Each infusion visit is relatively brief compared to many chemotherapy sessions, though you’ll typically spend additional time at the clinic for monitoring and any pre-medications.
Side Effects to Expect
Because Keytruda works by activating your immune system, its side effects are different from those of traditional chemotherapy. The main concern is immune-related adverse events, where the newly unleashed immune system attacks healthy tissue. In the KEYNOTE-355 trial, about 27% of patients treated with Keytruda experienced some form of immune-related side effect. Most were manageable: 5.3% were classified as severe (grade 3 or higher).
The most common immune-related problems involve the thyroid gland (causing either overactive or underactive thyroid), skin reactions, and inflammation in the lungs, liver, or intestines. These are typically caught through regular blood work and monitoring during treatment. Many can be managed by temporarily pausing Keytruda or using medications that calm the immune response. In some cases, if a serious immune-related event resolves, patients can resume Keytruda, though this decision is made on a case-by-case basis.
Keep in mind that because Keytruda is given alongside chemotherapy, you’ll also experience the standard side effects of chemo, including fatigue, nausea, and lowered blood counts. The combination means the overall side effect burden is real, and it’s worth discussing with your oncologist how to manage symptoms proactively throughout treatment.
Who Is Eligible
Eligibility depends on your specific diagnosis. For early-stage TNBC, Keytruda is approved for high-risk disease regardless of PD-L1 status. “High risk” generally refers to larger tumors or those that have spread to nearby lymph nodes. For metastatic or unresectable TNBC, your tumor must test positive for PD-L1 with a CPS of 10 or greater, determined by a specific FDA-approved lab test called PD-L1 IHC 22C3 pharmDx.
If you have a different subtype of breast cancer, such as hormone receptor-positive or HER2-positive, Keytruda is not currently approved for your disease. Some clinical trials are exploring immunotherapy in those subtypes, but there is no established evidence of benefit outside of TNBC at this time.