KEYNOTE-426: What the Kidney Cancer Trial Found

The argument this trial settled

Advanced kidney cancer is sorted into risk groups — favourable, intermediate and poor — using a scoring system built from lab results and how long ago the cancer was diagnosed.

When immune-based combinations first arrived, the evidence for them was strongest in intermediate and poor risk. For favourable-risk patients, who tend to do reasonably well on a targeted drug alone, it was genuinely unclear whether adding immunotherapy was worth the extra toxicity. KEYNOTE-426 reported a benefit across all three groups.

Two drugs against one

Field	Detail
Trial	KEYNOTE-426
Identifier	NCT02853331
Phase	Phase 3
Design	Randomised, open-label
Cancer type	Previously untreated advanced clear-cell kidney cancer
Comparator	Pembrolizumab by infusion every three weeks with axitinib tablets twice daily, against sunitinib tablets once daily
Primary endpoints	Overall survival and progression-free survival

861 people were randomised: 432 to the combination and 429 to sunitinib. Sunitinib was given on its usual schedule — daily for the first four weeks of each six-week cycle.

The two drugs in the combination do different jobs. Pembrolizumab releases a brake on the immune system. Axitinib attacks the blood vessels a tumour recruits to feed itself.

What the first interim analysis showed

At a median follow-up of 12.8 months, an estimated 89.9% of the combination group were alive at 12 months, against 78.3% on sunitinib. The hazard ratio for death was 0.53 (95% CI 0.38 to 0.74, p<0.0001).

Median progression-free survival was 15.1 months against 11.1 months, hazard ratio 0.69 (95% CI 0.57 to 0.84, p<0.001).

Tumours shrank in 59.3% of the combination group (95% CI 54.5 to 63.9) and 35.7% on sunitinib (95% CI 31.1 to 40.4), p<0.001.

The benefit held across the risk groups, and regardless of how much PD-L1 the tumour carried. That last point is why PD-L1 testing did not become a gatekeeper in kidney cancer the way it did in lung cancer.

Why a 12-month rate, and not a median

The headline survival figure is a landmark rate — the share alive at a fixed point — rather than a median. That is because at 12.8 months of follow-up, median survival had not been reached in either group. Fewer than half of each group had died, so there was no midpoint to report.

Landmark rates are honest but partial. They tell you where the curves sit at one moment and nothing about where they go afterwards.

Side effects when two drugs are combined

Severe side effects — grade 3 or higher, from any cause — occurred in 75.8% of the combination group and 70.6% of the sunitinib group.

Both figures are high. The gap between them is smaller than people often expect, because sunitinib is itself demanding. The practical difficulty with a combination is different: when something goes wrong, it is often unclear which drug caused it, and the answer changes what you stop.

What this trial cannot tell you

• What the median survival is. At this analysis it had not been reached in either arm.
• How this compares with other modern combinations. There was no arm giving two immune drugs together, so the trial cannot rank the options against each other.
• Anything about non-clear-cell kidney cancer. Only clear-cell disease was eligible.
• How a blinded trial would have read. This was open-label, and side-effect reporting is not immune to knowing your assignment.

Questions at a first kidney cancer treatment

• Which risk group am I in, and how was that worked out?
• If a side effect appears, how would you tell which drug is responsible?
• What are the alternatives to this particular pairing?

Sources

This article was written from the sources below, which were checked on the source-check date shown above.

• NEJM: Pembrolizumab plus Axitinib vs Sunitinib for Advanced Renal-Cell Carcinoma (KEYNOTE-426) (primary)

How this article was prepared

Prepared by Cancer Explained's AI-assisted editorial system and checked against the sources listed below. This article has not been reviewed by a healthcare professional unless a named reviewer is specifically shown.

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