Updated results from KEYNOTE-426 for metastatic kidney cancer

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Published: 12 Jun 2020
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Dr Elizabeth Plimack - Fox Chase Cancer Center, Philadelphia, USA

Dr Elizabeth Plimack talks to ecancer in an online interview for the ASCO virtual meeting 2020 about the KEYNOTE-426 study.

She outlines the trial design and explains the ongoing development of the study.

Dr Plimack discusses the updated results and maintained benefit of this combination.

At ASCO this year we presented updated results of the KEYNOTE-426 study. This is a randomised trial in patients with metastatic kidney cancer where they were randomised to receive axitinib and pembrolizumab versus sunitinib in the first line setting. The initial results of this trial were already presented and published last year when the trial met both primary endpoints of overall survival and progression free survival. We thought it was important to continue to present results over time so we can better describe the long-term impact of front-line treatment with axitinib and pembrolizumab on this patient population.

What we saw in these updated results is landmark analyses at one year and two years that show a higher percentage of patients alive as these time points than we’ve seen in the past and a maintained benefit of the axitinib pembrolizumab combination over sunitinib.

There has been some talk about the hazard ratio. The hazard ratio at this updated analysis seems to have settled out at 0.68. This is not quite as favourable as the hazard ratio at the initial analysis of 0.53 but I would point out it’s actually more important for a hazard ratio to start off good if it’s going to settle to a certain standard than to start off less discriminant between the two arms and then open up. It helps more patients. Those first few months include more patients and there are more patients who benefit. The landmark analysis of 426 really shows that.

One of the other exploratory investigations we did on this very large and valuable dataset is we looked at depth of response and its relationship to overall survival. When we separate out our patients in both arms of the study who survive to six months and we look at what their response was during those six months we then stratify them according to overall survival and find that the deeper the response the better their survival in the axitinib pembrolizumab arm, a relationship that did not hold true in the sunitinib arm.

This is more information that helps clinicians think about how to put into context the depth of their patients’ response. But ultimately I think what we see with this combination is almost all patients see their target lesions or tumours shrink. Most patients achieve benefit and that benefit seems to persist now at this updated follow-up at 24 months.