KEYNOTE-048
Made immunotherapy the first treatment for advanced head and neck cancer, alone for PD-L1-rich tumours and with chemotherapy for the rest.
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.
Setting
Untreated recurrent or metastatic HNSCC: pembrolizumab alone, pembrolizumab + platinum/5-FU, or cetuximab + platinum/5-FU (EXTREME)
Phase
Phase 3
Sponsor
Merck
Registry
Headline result
OS 14.9 vs 10.7 months (CPS ≥20, monotherapy); 13.0 vs 10.7 (all, with chemotherapy).
Reported
2019
Enrolled
882
Replication
CheckMate 141 (nivolumab, second line) showed the same direction; KEYNOTE-040 was borderline. Class effect of PD-1 blockade in HNSCC is consistent.
In plain words
What these results mean for people, not percentages
Overall survival, CPS ≥20, pembrolizumab monotherapyprimarysurvival endpoint
- Median 14.9 vs 10.7 months with Pembrolizumab compared with Cetuximab + chemotherapy; about 4.2 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 39 percent lower chance of the event at any given time (hazard ratio 0.61).
Overall survival, total population, pembrolizumab + chemotherapyprimarysurvival endpoint
- Median 13 vs 10.7 months with Pembrolizumab + chemotherapy compared with Cetuximab + chemotherapy; about 2.3 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 23 percent lower chance of the event at any given time (hazard ratio 0.77).
Be careful
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- These results apply to the people the trial enrolled: Untreated recurrent or metastatic HNSCC: pembrolizumab alone, pembrolizumab + platinum/5-FU, or cetuximab + platinum/5-FU (EXTREME). People in a different situation may not see the same effect.
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 participants enrolled.
Overall survival, CPS ≥20, pembrolizumab monotherapyprimary
HR 0.61
Pembrolizumab
14.9 mo
Cetuximab + chemotherapy
10.7 mo
Overall survival, total population, pembrolizumab + chemotherapyprimary
HR 0.77
Pembrolizumab + chemotherapy
13 mo
Cetuximab + chemotherapy
10.7 mo
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival, CPS ≥20, pembrolizumab monotherapyprimary | Pembrolizumab | — | 14.9 months | 0.61 | — | link |
| Cetuximab + chemotherapy | — | 10.7 months | ||||
| Overall survival, total population, pembrolizumab + chemotherapyprimary | Pembrolizumab + chemotherapy | — | 13 months | 0.77 | — | link |
| Cetuximab + chemotherapy | — | 10.7 months |
Replication
CheckMate 141 (nivolumab, second line) showed the same direction; KEYNOTE-040 was borderline. Class effect of PD-1 blockade in HNSCC is consistent.