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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.

Outcomes

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In plain words
What these results mean for people, not percentages
861 people took part
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
Source
Progression-free survivalprimary
HR 0.69
Pembrolizumab + axitinib
15.7 mo
Sunitinib
11.1 mo
EndpointArmnValueHR (95% CI)pSource
Overall survival (final, 5-year)primaryPembrolizumab + axitinib43247.2 months0.84 (0.71–0.99)link
Sunitinib42940.8 months
Progression-free survivalprimaryPembrolizumab + axitinib15.7 months0.69
Sunitinib11.1 months
Replication
Consistent with JAVELIN Renal 101 (avelumab + axitinib, PFS only), CheckMate 9ER, and CLEAR.

Connected

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