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Established immunotherapy plus chemotherapy as first-line treatment for metastatic triple-negative breast cancer with PD-L1 expression.
KEYNOTE-355, trial NCT02819518 sponsored by Merck and published in the New England Journal of Medicine in 2022, established pembrolizumab plus chemotherapy as first-line treatment for metastatic triple-negative breast cancer with PD-L1 expression. It randomised 847 patients and met its primary progression-free and overall survival endpoints in tumours with a combined positive score of ten or more, with no benefit below that threshold, which defined the PD-L1 cut-off used today. OnCo links it to triple-negative breast cancer, pembrolizumab, the CPS term, the TNBC roadmap and IMpassion131. It is now being succeeded by ADC-based first-line regimens such as ASCENT-04, and whether chemotherapy remains part of first-line treatment at all is the open question.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
882 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival, PD-L1 CPS ≥10primary | Pembrolizumab + chemotherapy | 220 | 23 months | 0.73 (0.55 to 0.95) | 0.0185 | link |
| Placebo + chemotherapy | 103 | 16.1 months | ||||
| Progression-free survival, PD-L1 CPS ≥10primary | Pembrolizumab + chemotherapy | - | 9.7 months | 0.66 (0.5 to 0.88) | - | link |
| Placebo + chemotherapy | - | 5.6 months | ||||
| Overall survival, CPS ≥1 | Pembrolizumab + chemotherapy | - | 17.6 months | 0.86 (0.72 to 1.04) | - | link |
| Placebo + chemotherapy | - | 16 months |
This is the population-based prevalence for the two label thresholds in early TNBC, and it shows the KEYNOTE-355 CPS 10 gate would admit only about a quarter of unselected patients.
PD-L1 testing with the combined positive score decides first-line treatment in metastatic triple-negative breast cancer; pembrolizumab-chemotherapy is the standard for scores of 10 or more.
The document that made immunotherapy, PARP inhibition and the first antibody-drug conjugate the European standard for metastatic triple-negative disease; every later first-line change is an amendment to it.
The clearest demonstration that PD-L1 positive in triple-negative breast cancer means different things depending on the kit; with atezolizumab withdrawn, pembrolizumab's 22C3 combined positive score of 10 is the surviving standard, and roughly a quarter of patients get a different answer depending on which assay their laboratory runs.
This is the paper Europe PMC returns for registry id NCT02819518 with the most citations, so it is the natural first reading for anyone following the KEYNOTE-355 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
Shares Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial, Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms, PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer, Combined positive score (CPS).
Shares Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial, KEYNOTE-355: pembrolizumab plus chemotherapy for PD-L1-positive advanced triple-negative breast cancer, Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms, PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer.
Shares Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms, Harmonise PD-L1 testing for triple-negative breast cancer around one scored assay, with external quality assurance, IMpassion130, PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer.
Shares ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer, KEYNOTE-119, ASCENT-04 / KEYNOTE-D19, TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line.
Shares IMpassion130, PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC).
Shares TROPION-Breast05, ASCENT-04 / KEYNOTE-D19, Triple-negative breast cancer (TNBC), Pembrolizumab.
Shares TROPION-Breast05, Combined positive score (CPS), Metastatic triple-negative breast cancer, Triple-negative breast cancer (TNBC).
Shares Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial, TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line, Triple-negative breast cancer (TNBC), Pembrolizumab.