KEYNOTE-426
The first immunotherapy plus targeted-pill combination for kidney cancer, improving survival across all risk groups.
OS HR 0.53 at first analysis; final (5-year) OS HR 0.84 with medians 47.2 vs 40.8 months; PFS 15.7 vs 11.1. FDA approval April 2019. Benefit attenuated over time as crossover to later-line immunotherapy accrued in the control arm.
Setting
Untreated advanced clear-cell RCC: pembrolizumab + axitinib vs sunitinib
Phase
Phase 3
Sponsor
Merck
Registry
Headline result
OS HR 0.84 final (47.2 vs 40.8 months); PFS HR 0.69.
Reported
2019
Enrolled
861
Replication
Consistent with JAVELIN Renal 101 (avelumab + axitinib, PFS only), CheckMate 9ER, and CLEAR.
In plain words
What these results mean for people, not percentages
Overall survival (final, 5-year)primarysurvival endpoint
- Median 47.2 vs 40.8 months with Pembrolizumab + axitinib compared with Sunitinib; about 6.4 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 16 percent lower chance of the event at any given time (hazard ratio 0.84, likely range 0.71 to 0.99).
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
Progression-free survivalprimarysurrogate endpoint
- Median 15.7 vs 11.1 months with Pembrolizumab + axitinib compared with Sunitinib; about 4.6 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 31 percent lower chance of the event at any given time (hazard ratio 0.69).
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
Be careful
- These results apply to the people the trial enrolled: Untreated advanced clear-cell RCC: pembrolizumab + axitinib vs sunitinib. 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.
861 participants enrolled.
Overall survival (final, 5-year)primary
HR 0.84 (0.71–0.99)
Pembrolizumab + axitinib
47.2 mo
Sunitinib
40.8 mo
Progression-free survivalprimary
HR 0.69
Pembrolizumab + axitinib
15.7 mo
Sunitinib
11.1 mo
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival (final, 5-year)primary | Pembrolizumab + axitinib | 432 | 47.2 months | 0.84 (0.71–0.99) | — | link |
| Sunitinib | 429 | 40.8 months | ||||
| Progression-free survivalprimary | Pembrolizumab + axitinib | — | 15.7 months | 0.69 | — | — |
| Sunitinib | — | 11.1 months |
Replication
Consistent with JAVELIN Renal 101 (avelumab + axitinib, PFS only), CheckMate 9ER, and CLEAR.