WINTHER

WINTHER was run by the WIN Consortium, an international network founded around Gustave Roussy, and enrolled 303 patients between 2013 and 2015 at Gustave Roussy, Vall d'Hebron, Sheba Medical Center, McGill and UC San Diego. Each patient had a tumour biopsy and a matched normal tissue biopsy. Arm A used DNA sequencing (Foundation Medicine's panel) to match a targeted drug; patients with no DNA match moved to arm B, where a transcriptomic algorithm ranked drugs by the difference in gene expression between the tumour and the normal tissue. In all, 107 patients were treated, 69 in the DNA arm and 38 in the RNA arm.

The primary endpoint, comparing each patient's progression-free survival on study therapy with their progression-free survival on their previous line of treatment, was not met in either arm, so the trial is formally negative. The Nature Medicine report in 2019 nonetheless showed that RNA-based matching was feasible at scale across countries, that treatment recommendations could be produced within a clinically useful time, and that a higher matching score and less prior therapy were associated with longer progression-free survival, echoing I-PREDICT.

WINTHER's lasting effects are methodological: it normalised matched-normal biopsies, showed transcriptomics can widen the pool of patients with a rational option, and informed the design of later WIN Consortium trials that combine DNA, RNA and immune profiling. It also illustrated how hard it is to prove benefit with a within-patient comparison rather than a randomised control.