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July 31, 2026 precision-oncology basket-trials evidence

DRUP: a basket trial does not make all biomarkers equally strong

Cohorts in the Dutch DRUP programme produced sharply different outcomes. The contrast is not evidence that actionability tiers do not matter; its own later analysis argues that strong biological and prior clinical evidence tracked with the better-performing targets.

Written retrospectively and published on August 3, 2026.

Background reading, not clinical guidance. This describes published research; it is not a recommendation for any individual case, and the cited studies may have been superseded.

Drug rediscovery trials test approved cancer drugs outside their usual indication when a tumour has a potentially relevant molecular feature. They are an efficient way to learn, but their inclusion rule is broader than a guarantee that every drug–biomarker pair is equally convincing.

DRUP’s tumour-agnostic cohort of microsatellite-instable tumours treated with nivolumab reported a clinical benefit rate of 63%. By contrast, palbociclib or ribociclib alone in cancers with cyclin D–CDK4/6-pathway alterations had a 16-week clinical benefit rate of 15% and an objective response rate of 0% in a pooled DRUP and MoST analysis.

Keep the endpoints straight

Both headline percentages are clinical benefit rates, not response rates. They count either a confirmed response or stable disease lasting at least sixteen weeks. Calling the 15% figure a response rate would turn a zero-response cohort into a misleadingly positive one.

The lesson is not that formal evidence levels fail to predict outcomes. A 2026 DRUP analysis concluded that high-performing targets shared strong biological rationale and prior clinical activity, whereas some weaker biomarkers had modest activity. Equal access to a basket-trial cohort is not equal evidence.

Sources

  1. van der Velden DL, Hoes LR, van der Wijngaart H, et al. The Drug Rediscovery Protocol facilitates the expanded use of existing anticancer drugs. Nature. 2019. · 10.1038/s41586-019-1600-x
  2. Zeverijn LJ, Looze EJ, Thavaneswaran S, et al. Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations. International Journal of Cancer. 2023. · 10.1002/ijc.34649
  3. Verkerk K, Spiekman AC, Haj Mohammad SF, et al. Prospective evaluation of genomics-guided off-label treatment. Nature. 2026. · 10.1038/s41586-026-10405-x

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