KEYNOTE-426

Clinical question

In previously untreated advanced clear-cell RCC, does pembrolizumab plus axitinib improve outcomes over sunitinib?

Trial context

Population

861 patients

Intervention

Pembrolizumab 200 mg IV q3w up to 35 cycles + axitinib 5 mg PO BID; control sunitinib 50 mg PO daily 4 weeks on/2 weeks off.

Comparator

Sunitinib

Primary / key evidence

12-mo OS 89.9% vs 78.3% (+11.6 pp); HR death 0.53. Median PFS 15.1 vs 11.1 mo; ORR 59.3% vs 35.7%.

Absolute Effect

What changes for patients?

12-mo OS 89.9% vs 78.3% (+11.6 pp); HR death 0.53. Median PFS 15.1 vs 11.1 mo; ORR 59.3% vs 35.7%.

NNT/NNH: Not calculated unless a defensible fixed-time event-rate comparison was available in the cited primary analysis; median-survival differences alone are not converted to NNT.

Clinical interpretation

The combination improved OS, PFS and response compared with sunitinib in first-line advanced ccRCC.

Limitations / maturity

Interpret the effect in the context of the trial population, endpoint definition, follow-up and treatment era. Subsequent trials and evolving standards may limit direct applicability to contemporary patients.

Primary publication

Rini BI et al. N Engl J Med. 2019;380:1116–1127.

Primary publication / source

← Return to The Absolute Effect

Current-practice context · reviewed 14 October 2026

Where this trial fits now

Pembrolizumab/axitinib remains one established first-line IO–TKI option in advanced clear-cell RCC. Its pivotal comparison was against sunitinib; it does not establish superiority over other contemporary combinations. For IMDC favorable-risk patients, long-term evidence has shown PFS/response benefit without a clear OS advantage versus sunitinib, so individualize choice against other approved regimens and TKI monotherapy where guideline-supported.

EAU RCC disease-management guidance ↗

Targeted freshness note added 14 October 2026; exhaustive guideline reconciliation remains pending.