CLEAR (KEYNOTE-581)
The combination with the longest progression-free survival ever reported in first-line kidney cancer, at nearly two years.
PFS 23.9 vs 9.2 months (HR 0.39); ORR 71% with 16% complete responses; final OS HR 0.79 (medians 53.7 vs 54.3 months, curves separating late). FDA approval August 2021. Lenvatinib dosing (20 mg) drives high toxicity and dose reductions (~70%).
Setting
Untreated advanced clear-cell RCC: lenvatinib + pembrolizumab vs sunitinib (and lenvatinib + everolimus arm)
Phase
Phase 3
Sponsor
Eisai / Merck
Registry
Headline result
PFS 23.9 vs 9.2 months (HR 0.39); OS HR 0.79.
Reported
2021
Enrolled
1069
Replication
Consistent with other IO-TKI doublets; lenvatinib-everolimus arm improved PFS but not OS versus sunitinib.
In plain words
What these results mean for people, not percentages
Progression-free survivalprimarysurrogate endpoint
- Median 23.9 vs 9.2 months with Lenvatinib + pembrolizumab compared with Sunitinib; about 14.7 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 61 percent lower chance of the event at any given time (hazard ratio 0.39, likely range 0.32 to 0.49).
- 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.
Overall survival (final)survival endpoint
- Median 53.7 vs 54.3 months with Lenvatinib + pembrolizumab compared with Sunitinib; about 0.6 months shorter 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 21 percent lower chance of the event at any given time (hazard ratio 0.79, likely range 0.63 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.
Be careful
- These results apply to the people the trial enrolled: Untreated advanced clear-cell RCC: lenvatinib + pembrolizumab vs sunitinib (and lenvatinib + everolimus arm). 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.
1,069 participants enrolled.
Progression-free survivalprimary
HR 0.39 (0.32–0.49)
Lenvatinib + pembrolizumab
23.9 mo
Sunitinib
9.2 mo
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survivalprimary | Lenvatinib + pembrolizumab | 355 | 23.9 months | 0.39 (0.32–0.49) | — | link |
| Sunitinib | 357 | 9.2 months | ||||
| Overall survival (final) | Lenvatinib + pembrolizumab | — | 53.7 months | 0.79 (0.63–0.99) | — | link |
| Sunitinib | — | 54.3 months |
Replication
Consistent with other IO-TKI doublets; lenvatinib-everolimus arm improved PFS but not OS versus sunitinib.cancers
1drugs
4ApprovedSmall-molecule mTOR inhibitor
Everolimus · Afinitor
ApprovedSmall-molecule multi-kinase inhibitor (VEGFR, FGFR, PDGFR, RET, KIT)
Lenvatinib · Lenvima
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
ApprovedSmall-molecule multi-kinase inhibitor (VEGFR, PDGFR, KIT)
Sunitinib · Sutent