# KEYNOTE-048

Source: https://onco.cc/trials/keynote-048/  
OnCo record `keynote-048` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Made immunotherapy the first treatment for advanced head and neck cancer, alone for PD-L1-rich tumours and with chemotherapy for the rest.

## Summary

Pembrolizumab monotherapy improved OS in CPS ≥20 (14.9 vs 10.7 months) and CPS ≥1 (12.3 vs 10.3); pembrolizumab-chemotherapy improved OS in the total population (13.0 vs 10.7). FDA approval June 2019. Five-year follow-up confirmed durable survival tails. Replaced the EXTREME regimen as first line after a decade.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT02358031
- Phase: 3
- Setting: Untreated recurrent or metastatic HNSCC: pembrolizumab alone, pembrolizumab + platinum/5-FU, or cetuximab + platinum/5-FU (EXTREME)
- Sponsor: Merck
- Enrolled: 882
- Result: OS 14.9 vs 10.7 months (CPS ≥20, monotherapy); 13.0 vs 10.7 (all, with chemotherapy).
- Outcomes: Overall survival, CPS ≥20, pembrolizumab monotherapy: Pembrolizumab 14.9 months vs Cetuximab + chemotherapy 10.7 months, HR 0.61; Overall survival, total population, pembrolizumab + chemotherapy: Pembrolizumab + chemotherapy 13 months vs Cetuximab + chemotherapy 10.7 months, HR 0.77
- Replication: CheckMate 141 (nivolumab, second line) showed the same direction; KEYNOTE-040 was borderline. Class effect of PD-1 blockade in HNSCC is consistent.

## Sources

- ClinicalTrials.gov NCT02358031: https://clinicaltrials.gov/study/NCT02358031
- Lancet 2019: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32591-7/fulltext

## Connected records

- cancers: [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer)](https://onco.cc/cancers/hpv-negative-head-and-neck-cancer/), [HPV-positive oropharyngeal cancer](https://onco.cc/cancers/hpv-positive-oropharyngeal-cancer/), [Hypopharyngeal cancer](https://onco.cc/cancers/hypopharyngeal-cancer/), [Laryngeal and hypopharyngeal cancer](https://onco.cc/cancers/laryngeal-cancer/), [Lip cancer](https://onco.cc/cancers/lip-cancer/), [Oral cavity cancer (mouth and tongue)](https://onco.cc/cancers/oral-cavity-cancer/), [Oral tongue and floor of mouth cancer](https://onco.cc/cancers/oral-tongue-cancer/), [Oropharyngeal cancer (tonsil and base of tongue)](https://onco.cc/cancers/oropharyngeal-cancer/), [Recurrent or metastatic head and neck squamous cell carcinoma](https://onco.cc/cancers/recurrent-metastatic-hnscc/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- terms: [Combined positive score (CPS)](https://onco.cc/terms/cps/)
- trials: [EXTREME](https://onco.cc/trials/extreme/)
- people: [Barbara Burtness](https://onco.cc/people/barbara-burtness/)
- ideas: [Photoimmunotherapy as an in situ vaccine with PD-1 blockade](https://onco.cc/ideas/idea-photoimmunotherapy-plus-pd1/), [Test one-tenth-dose immunotherapy where the full dose is unaffordable](https://onco.cc/ideas/idea-cost-low-dose-immunotherapy-trials/)
- bottlenecks: [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/)

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