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FDA Approval: Pembrolizumab (Keytruda) for Melanoma
FDA approved Pembrolizumab (Keytruda), an anti-PD-1 checkpoint inhibitor, for certain people with melanoma. What was approved, the evidence, and what it does and doesn't mean.
Original commentary from the Cancer Explained editorial team.
Historical context: this page explains an event dated 2014. It was published as an explainer on July 12, 2026 and is not breaking news.
Please note: this page is educational only — it is not medical advice, and it does not speculate about anyone’s health beyond reliable public reporting. For questions about your own health, talk with your healthcare team.
The drug that took the brakes off
Pembrolizumab, sold as Keytruda, is a programmed death receptor-1 blocking antibody. Almost everyone shortens that to PD-1.
FDA records show its first approval, under biologic license 125514, on September 4, 2014, under priority review. Melanoma was the first cancer it was cleared for. The label still carries an Initial U.S. Approval date of 2014.
T cells carry PD-1 on their surface. When PD-1 is engaged, the T cell powers down. That switch keeps the immune system from attacking healthy tissue, and some tumors use it to stay hidden. Pembrolizumab blocks the receptor so the switch cannot be pulled. Our page on immunotherapy covers the wider family of these drugs.
What the melanoma label covers now
The label has grown well past that first indication. For melanoma it has two entries.
The first is treatment of melanoma that cannot be removed by surgery, or that has spread. The second is adjuvant treatment, meaning treatment given after surgery has removed everything visible, for adults and children aged 12 and older with stage IIB, IIC or III melanoma following complete resection.
For melanoma it is given every 3 weeks, or on a longer schedule of every 6 weeks. For children the amount is worked out from body weight, up to a ceiling, every 3 weeks.
The trial in advanced disease
KEYNOTE-006 was a randomized, open-label trial in 834 people with melanoma that could not be removed or had spread. It compared pembrolizumab against ipilimumab, the checkpoint drug already in use.
Deaths were 33 percent in one pembrolizumab arm and 30 percent in the other, against 40 percent with ipilimumab. The hazard ratios for overall survival were 0.69 and 0.63.
Progression-free survival improved too, with a hazard ratio of 0.58 in both arms. Median progression-free survival was 4.1 and 5.5 months, against 2.8 months.
About a third of people responded, at 33 and 34 percent, against 12 percent with ipilimumab. Complete responses were 6 and 5 percent.
The point worth holding onto is that this trial measured overall survival, which counts deaths rather than scan findings. Many approvals do not.
The trials after surgery
KEYNOTE-054 enrolled 1,019 people whose stage IIIA, IIIB or IIIC melanoma had been fully removed. They received pembrolizumab or placebo for up to a year.
Recurrence happened in 26 percent on the drug and 43 percent on placebo, a hazard ratio of 0.57. Spread to distant organs happened in 34 percent against 49 percent, a hazard ratio of 0.60.
KEYNOTE-716 did the same for earlier disease, stage IIB and IIC, in 976 people. Recurrence occurred in 11 percent against 17 percent, a hazard ratio of 0.65.
Both trials measured recurrence, not survival. That is a real result about how often the cancer comes back. It is not the same claim as living longer. Our page on melanoma stages explains what these stage labels describe.
What can go wrong
The leading warning on the label is immune-mediated adverse reactions. Releasing a brake on the immune system can let it attack healthy organs, and the label says these reactions may be severe or fatal and can occur in any organ system.
Named examples include pneumonitis, colitis, hepatitis, hormone-gland problems, kidney inflammation, skin reactions, and rejection of a transplanted organ.
Monitoring is specified. Liver enzymes, creatinine and thyroid function are checked at the start and from time to time during treatment.
In KEYNOTE-054, serious reactions occurred in 25 percent of people on the drug, and 14 percent stopped it permanently. The most common reasons for stopping were pneumonitis, colitis and diarrhea. Hypothyroidism occurred in 15 percent against 2.8 percent on placebo.
New breathlessness, persistent diarrhea, a rash, or unusual fatigue during treatment are reasons to call the team rather than wait. Our page on immunotherapy side effects covers what to report and when.
When to get checked
Melanoma is a skin cancer, and the earliest sign is usually a mole that changes. NCI gives the ABCDE list.
- Asymmetry: one half does not match the other.
- Border: edges are irregular.
- Color: more than one color in the same spot.
- Diameter: usually larger than 6 millimeters.
- Evolving: the mole changes in size, shape or color over time.
NCI also flags a mole that itches, oozes, bleeds or breaks down, a change in pigmented skin, and new moles growing near an existing one.
The group picture
SEER figures describe the whole United States population, not one person.
Five-year relative survival for melanoma of the skin is 94.7 percent for cases from 2016 to 2022. By stage it is 100.0 percent while confined to the original site, 76.0 percent once it has reached nearby lymph nodes, and 34.0 percent once it has spread further.
Seventy-seven percent are found at that first stage, which is why the overall figure is so high. Five percent are already distant. An estimated 112,000 new cases and 8,510 deaths are projected for 2026 by the American Cancer Society.
What this approval cannot tell you
An approval sets out who is eligible in general terms. Whether it fits a particular person depends on stage, other health conditions, and autoimmune history. The adjuvant trials excluded people with active autoimmune disease and people with mucosal or ocular melanoma.
A hazard ratio describes a group across years of follow-up. It does not predict one person's course.
And an approval is a decision about evidence, not a promise of benefit. Labels change as more data arrive, and this one has changed many times since 2014.
Sources
- DailyMed, KEYTRUDA (pembrolizumab) prescribing information — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287
- FDA Drugs@FDA, pembrolizumab (BLA 125514) — https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125514
- openFDA Drugs@FDA API, BLA125514 submission record (ORIG-1, 2014-09-04, priority review) — https://api.fda.gov/drug/drugsfda.json?search=openfda.application_number:%22BLA125514%22&limit=1
- NCI, Pembrolizumab — https://www.cancer.gov/about-cancer/treatment/drugs/pembrolizumab
- NCI PDQ, Melanoma Treatment (Patient Version) — https://www.cancer.gov/types/skin/patient/melanoma-treatment-pdq
- SEER Cancer Stat Facts, Melanoma of the Skin — https://seer.cancer.gov/statfacts/html/melan.html
How this article was prepared
An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.
The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.
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Put the story in context
Prevention, possible warning signs, screening, and diagnosis
This story relates to Melanoma. The information below is general: it does not reveal anything else about a public person’s health, and not every point applies to every cancer. Personal advice depends on age, symptoms, family history, exposures, and medical history.
Prevention and risk reduction
Not every cancer can be prevented. Avoiding tobacco, protecting skin from ultraviolet radiation, limiting alcohol, staying active, and receiving recommended HPV or hepatitis B vaccination can lower the risk of certain cancers. A risk factor is not a prediction or a cause in one individual.
Symptoms and possible early signs
Possible signs vary and are often caused by conditions other than cancer. Changes worth discussing include a new lump, unexplained bleeding or weight loss, a persistent cough, lasting bowel or bladder changes, a changing skin spot, or symptoms that persist or worsen. Some early cancers cause no symptoms.
Screening and early detection
Screening looks for certain cancers before symptoms begin. Recommended tests exist only for some cancers and depend on age and risk. Screening can have benefits and harms; it is not the same as evaluating a new symptom, and there is no single routine scan or blood test that reliably screens for every cancer.
How cancer is diagnosed
Diagnosis may involve a history and exam, imaging, laboratory tests, and often a biopsy. Pathology can identify the cancer type and may test biomarkers that guide treatment. Symptoms, screening results, tumor markers, or online stories alone cannot confirm cancer.
Learn about this story’s cancer topic
A public story may encourage questions, but it should not be used to estimate your risk or choose testing. Contact a healthcare professional about a persistent or concerning change. Seek urgent care for severe or rapidly worsening symptoms.