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KEYNOTE-355: What the Breast Cancer Trial Found
KEYNOTE-355 tested pembrolizumab with chemotherapy in metastatic triple-negative breast cancer. The benefit showed up only in tumors with a PD-L1 score of 10 or more. Here is what each group saw.
Original commentary from the Cancer Explained editorial team.
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.
A drug that helps some people and not others
Triple-negative breast cancer has no hormone receptors and no HER2 to aim at, so chemotherapy has long been the mainstay. KEYNOTE-355 asked whether adding the immune drug pembrolizumab helps. The honest answer depends entirely on one lab score.
What a PD-L1 combined positive score is
Pathologists stain the tumor for PD-L1, a protein that helps cancer cells avoid the immune system. The combined positive score, or CPS, counts the stained tumor cells, lymphocytes and macrophages, divides by the number of live tumor cells, and multiplies by 100.
A CPS of 10 or more means a lot of staining. The trial planned in advance to look at three groups: CPS 10 or more, CPS 1 or more, and everyone.
Who took part
847 people joined, at 209 sites in 29 countries. All had triple-negative breast cancer that was metastatic, or had come back and could not be removed by surgery. None had been treated for advanced disease yet. 566 were assigned to pembrolizumab with chemotherapy and 281 to a placebo with chemotherapy.
The chemotherapy was not fixed. It could be nab-paclitaxel, paclitaxel, or gemcitabine with carboplatin.
Results, group by group
In the CPS 10 or more group, the cancer was held off for a median of 9.7 months with pembrolizumab and 5.6 months without. Hazard ratio 0.65 (95% CI 0.49 to 0.86; one-sided p=0.0012). That met the target set in advance.
In the CPS 1 or more group the gap narrowed to 7.6 against 5.6 months (hazard ratio 0.74; 95% CI 0.61 to 0.90), which missed the trial's strict threshold. Across everyone it was 7.5 against 5.6 months (hazard ratio 0.82; 95% CI 0.69 to 0.97), not formally tested.
Severe side effects were near identical: grade 3 to 5 treatment-related events in 68% against 67%.
The survival report that followed
A later report gave overall survival after a median follow-up of 44.1 months.
In the CPS 10 or more group, median survival was 23.0 months against 16.1 months (hazard ratio 0.73; 95% CI 0.55 to 0.95; p=0.0185). In the CPS 1 or more group it was 17.6 against 16.0 months (hazard ratio 0.86), which was not significant. Across everyone it was 17.2 against 15.5 months (hazard ratio 0.89), and significance was not tested.
The pattern is consistent. The more PD-L1 a tumor shows, the more the immune drug appears to do.
What to keep in perspective
- Outside the CPS 10 or more group, no survival benefit was proven. That is the finding, not a gap in the data.
- Even in the best group, the median moved from about 16 months to about 23. This is still an incurable setting.
- Three different chemotherapy partners were allowed, which makes the comparison less clean than it looks.
- CPS is measured on a biopsy at one moment. Scores can differ between samples.
Questions about PD-L1 testing in triple-negative breast cancer
- What is my CPS, and which sample was it measured on?
- If my CPS is below 10, what does that mean for my options?
- Which chemotherapy would be used alongside, and why that one?
- What are the signs of an immune-related side effect I should call about?
Sources
This article was written from the sources below, which were checked on the source-check date shown above.
- Lancet: Pembrolizumab plus chemotherapy vs placebo plus chemotherapy for previously untreated locally recurrent/metastatic TNBC (KEYNOTE-355) (primary)
- NEJM: Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer (KEYNOTE-355 overall survival) (primary)
How this article was prepared
Prepared by Cancer Explained's AI-assisted editorial system and checked against the sources listed below. This article has not been reviewed by a healthcare professional unless a named reviewer is specifically shown.
Cancer Explained is published by the National Cancer Information Foundation as a nonprofit-oriented public-interest education project. It is not a diagnostic service, does not recommend treatments, and is not for emergencies.
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Prevention, possible warning signs, screening, and diagnosis
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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.
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