The largest published prospective evaluation of an off-label targeted cancer therapy shows that more patients may benefit from existing drugs. After enrolling more than 1,600 patients in the Dutch multicenter DRUP trial, the team presented their results: nature today. “Our findings highlight the fact that effective off-label use is possible, but should only be done within the setting of a clinical trial.”
The pan-cancer DRUP trial aims to enable more individualized treatment options by expanding the use of existing drugs beyond their approved indications. Over the past 10 years, this trial has provided off-label treatment opportunities to more than 1,600 patients with advanced cancer for whom no standard treatment remains. The results presented today show that this strategy can provide significant benefits to patients.
lasting effect
Participants received existing drugs registered against other types of cancer with more common DNA profiles. About one-third of patients responded to treatment or had stable disease for at least four months. Overall survival was 8 months, and approximately 1 in 4 patients experienced serious side effects.
Importantly, 67 exceptional responders emerged across different molecular subgroups who demonstrated a complete response or remained progression-free for at least 2 years. This indicates that these targeted drugs have the potential to provide deep and lasting benefits even in well-pretreated, difficult-to-treat, or rare cancers.
Access to medicines
To unlock this potential, “off-label anticancer drugs should only be prescribed within the framework of a systematic evaluation of efficacy and toxicity,” says Emil Vorst, principal investigator at the Netherlands Cancer Institute and the Oncode Institute. “Oncologists often treat patients with off-label therapies outside of clinical trial settings, which carry significant risks of toxicity, cost, and uneven access.”
In addition to preventing unnecessary side effects caused by ineffective treatments, systematic data collection and analysis can also expand patient access to medicines by allowing label extensions when efficacy is clear. One DRUP expansion cohort provided sufficient evidence to achieve full national reimbursement for a new treatment option for patients with MSI tumors.
DRUP-like protocols
This trial grew a European network of investigator-initiated trials using similar DRUP-like protocols. This will create a valuable source of evidence, especially for patients with rare cancers who have limited treatment options and clinical trial opportunities. Previous analyzes of DRUP data have shown that comprehensive molecular testing in patients with rare cancers may identify treatment opportunities and clinical benefits similar to those in patients with common cancers.
The study was led by principal investigators Emile Voest (NKI), Henk Verheul (Erasmus MC Cancer Institute) and Hans Gelderblom (LUMC). This study was funded by KWF Dutch Cancer Society and Stelvio for Live. The Emile Voest Group is part of the Oncode Institute.
sauce:
Dutch Cancer Institute
Reference magazines:
Verkerk, K. others. (2026). Prospective evaluation of genomics-based off-label treatments. nature. DOI: 10.1038/s41586-026-10405-x. https://www.nature.com/articles/s41586-026-10405-x
