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KEYNOTE-412 tested adding pembrolizumab to standard chemoradiotherapy for locally advanced head and neck cancer; the improvement in keeping patients free of disease fell short of statistical significance, so chemoradiotherapy alone remains the standard.
KEYNOTE-412 randomised 804 patients with newly diagnosed locally advanced head and neck squamous cell carcinoma (oropharynx, larynx or hypopharynx, and oral cavity) to pembrolizumab or placebo given as a priming dose before, concurrently with and for a year after cisplatin-based chemoradiotherapy. The primary endpoint was event-free survival.
Event-free survival favoured pembrolizumab but the difference did not reach the prespecified threshold for statistical significance, with a larger effect in PD-L1-high tumours in exploratory analysis. Together with the negative JAVELIN Head and Neck 100 trial of avelumab, it showed that concurrent checkpoint blockade does not reliably add to definitive chemoradiotherapy, in contrast to the success of neoadjuvant and adjuvant pembrolizumab around surgery in KEYNOTE-689.
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.
804 enrolled.
Not reached (95% CI 44.7 months to not reached); median follow-up 47.7 months
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Event-free survivalprimary | Pembrolizumab + chemoradiotherapy | 402 | Not reached (95% CI 44.7 months to not reached); median follow-up 47.7 months | 0.83 (0.68 to 1.03) | 0.043 (significance threshold 0.024) | link |
| Placebo + chemoradiotherapy | 402 | 46.6 months | ||||
| Grade 3 or worse adverse events | Pembrolizumab + chemoradiotherapy | 398 | 92% | - | - | link |
| Placebo + chemoradiotherapy | 398 | 88% | ||||
| Serious adverse events | Pembrolizumab + chemoradiotherapy | 398 | 62% | - | - | link |
| Placebo + chemoradiotherapy | 398 | 49% |
Shares Merck & Co. (MSD), Cisplatin, Pembrolizumab, Immune checkpoint inhibitors and the tag subtype-trials.
Shares Merck & Co. (MSD), Cisplatin, Pembrolizumab, Immune checkpoint inhibitors and the tag subtype-trials.
Shares Merck & Co. (MSD), Pembrolizumab, Immune checkpoint inhibitors and the tag subtype-trials.
Shares Merck & Co. (MSD), Pembrolizumab, Immune checkpoint inhibitors and the tag subtype-trials.
Shares Cisplatin, Immune checkpoint inhibitors and the tag subtype-trials.
Shares Merck & Co. (MSD), Pembrolizumab, Immune checkpoint inhibitors and the tag subtype-trials.
Shares Pembrolizumab, Immune checkpoint inhibitors and the tag subtype-trials.
Shares Cisplatin, Head and neck squamous cell carcinoma and the tag subtype-trials.