Dutch study shows off-label targeted therapies benefit more cancer patients

The largest published prospective evaluation of off-label targeted cancer therapies has shown that more patients could benefit from existing drugs. After including over 1600 patients in the Dutch multicenter DRUP trial, the team publishes the results in Nature today. "Our findings underscore the fact that effective off-label use is possible, but should only be done within clinical trial settings."

The pan-cancer DRUP trial seeks to realize more personalized treatment options by expanding the use of existing drugs beyond their approved indication. Over the past 10 years, the trial has provided off-label treatment opportunities to over 1600 patients with advanced cancers without remaining standard therapies. The results published today demonstrate that this strategy can offer patients substantial benefit.

Durable effect

Participants received existing drugs that have been registered for other cancer types in which their DNA profile is more common. About one third of the patients responded to the treatment or had stable disease for at least four months. The overall survival was 8 months and roughly 1 in 4 patients experienced serious side effects.

Importantly, 67 exceptional responders emerged across different molecular subgroups, showing a complete response or remaining progression-free for at least two years. This illustrates the potential of these targeted drugs to deliver profound and durable benefit, even heavily pretreated, difficult-to-treat or rare cancers.

Access to medicines

In order to unlock this potential, "Off-label anticancer drugs should only be prescribed within frameworks that systematically evaluate efficacy and toxicity", says principle investigator Emile Voest from the Netherlands Cancer Institute and Oncode Institute. "Oncologists often treat patients with off-label treatments outside trial settings. This involves significant risks of toxicity, costs and uneven access."

Apart from preventing unnecessary side effects caused by ineffective treatments, systematic data capturing and analysis can also expand patients' access to medicines by enabling label expansion when efficacy is clear. One DRUP expansion cohort generated sufficient evidence to achieve full national reimbursement for a new treatment option for patients with MSI tumors.

DRUP-like protocols

The trial has given rise to a growing European network of investigator-initiated trials with similar, DRUP-like protocols. This will build an invaluable source of evidence, in particular for patients with rare cancers, who face limited treatment options and trial opportunities. Earlier analysis of DRUP-data showed that comprehensive molecular testing in patients with rare cancers may identify treatment opportunities and clinical benefit similar to 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 research was financially supported by KWF Dutch Cancer Society and Stelvio for Live. The Emile Voest group is part of Oncode Institute.