A large prospective evaluation of off-label targeted cancer therapies has shown that more patients could potentially benefit from existing drugs. After including over 1,600 patients in the Dutch multicenter Drug Rediscovery Protocol (DRUP) trial (ClinicalTrials.gov identifier NCT02925234), the research team has published their findings in Nature. “Our findings underscore the fact that effective off-label use is possible but should only be done within clinical trial settings,” Verkerk et al wrote.
The pancancer DRUP trial is seeking 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 patients with advanced cancers without remaining standard therapies.
Durable Effects With Off-Label Options
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 4 months. The overall survival was 8 months, and roughly one-quarter of the 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 2 years. This illustrates the potential of these targeted drugs to deliver profound and durable benefit, even in heavily pretreated, difficult-to-treat, or rare cancers.
In order to unlock this potential, “Off-label anticancer drugs should only be prescribed within frameworks that systematically evaluate efficacy and toxicity,” said principal investigator Emile Voest, MD, of the Netherlands Cancer Institute and Oncode Institute. “Oncologists often treat patients with off-label treatments outside trial settings. This involves significant risks of toxicity, cost, 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 microsatellite-instable tumors.
Growing Interest in Protocol
The trial has given rise to a growing European network of investigator-initiated trials with similar, DRUP-like protocols. This will hopefully build an invaluable source of evidence 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.
DISCLOSURE: This research was financially supported by KWF Dutch Cancer Society and Stelvio for Live. For full disclosures of the study authors, visit nature.com.
