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Cancer Patients Could Benefit From “Off-label” Drugs
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Cancer Patients Could Benefit From “Off-label” Drugs

Cancer Patients Could Benefit From “Off-label” Drugs
News

Cancer Patients Could Benefit From “Off-label” Drugs

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Some cancer patients may benefit from being treated with “off-label” drugs that are not routinely prescribed for their exact tumor type, according to new research conducted as part of the Drug Rediscovery protocol. Findings were published in Nature September 30, 2019.

“There are potential opportunities for patients to benefit from drugs that already exist, and it may not actually be necessary to develop new drugs. Therefore, you can start testing these existing drugs almost immediately – that was the basis for starting this study,” explains Emile Voest, senior author of the study. 

The Drug Rediscovery protocol – An adaptive, precision-oncology trial


The purpose of the Drug Rediscovery protocol is to determine the treatment efficacy of anticancer drugs for advanced cancers outside of their approved label in patients harboring alterations that can potentially be targeted by these drugs.

To be eligible for the trial the cancer patients had to either:

  • No longer benefit from a standard anticancer treatment or
  • Have a cancer for which no such treatment is available or indicated.


Eligible patients with a potentially actionable genetic or molecular variant were matched to one of the “off-label” anticancer drugs in the study.

“The good news is, is that there are already many, many drugs on the shelf that are approved by the [US Food and Drug Administration] (FDA) or [
European Medicines Agency] (EMA). For the drugs that have been developed, we know that certain drugs work in certain tumor types. By having a national program of large-scale sequencing, we identified that 13% of patients have a molecular target where we have such a drug,” says Voest.

What does “off-label” mean?

Before a drug is approved and made available to patients, it undergoes rigorous preclinical and clinical testing to confirm that it:

  • is effective at treating a specific medical condition
  • works the way it is expected to
  • is safe to use


Evidence of this testing is submitted to the regulatory authorities (e.g. the US Food and Drug Administration (FDA)) which is then considered, and approval is granted if they are satisfied with the information provided. The drug is then given an official “drug label” – defining its approved indication, recommended dosage, and method of administration.

When a drug is given to a patient in a format that deviates from the drug label it is said to be “off-label” use.

Findings from the first 215

“Every patient with metastatic cancer, deserves to have diagnostic work or whole genome sequencing performed to make sure that we can identify old targets that are potentially helpful to the patient,” say Voest.


"We have shown that during the metastatic behavior of a tumor, the key targets remain there. It is different if you look at the primary tumor versus metastases, as there are differences, but once the cancer has metastasized, the key drivers are maintained."

Velden, et al. studied the first 215 treated patients. Sixty three percent received targeted therapies [n=136], and the remaining 37% received immunotherapy [n=79]. Their results demonstrate that 34% of the 215 patients showed a clinical benefit – defined as complete or partial response or disease stability after 16 weeks.

The authors do note some limitations of the current study. One important limitation is the absence of comparator groups, due to the non-randomized trial design. In addition, the heterogeneous study population makes “correct interpretation of molecular aberrations challenging.” The authors also mention that whilst it was possible to detect tumor growth or a reduction in tumor size, it was not possible to detect reductions in the rate of growth.

Voest touches on their progress: “What we present in the Nature paper is indeed the first analysis of which we had sufficiently long follow up – at least four months. At the moment, we have registered and reviewed over 1000 patients, and we have more than 450 patients under treatment. The data are not mature yet – but we are making progress and creating lots of opportunities for patients.” 

Driving precision medicine forward

The Drug Rediscovery protocol aims to identify early signals of activity in these patients, accelerate the clinical translation of these insights into the use of drugs outside of their drug label, and create a repository of data that can be used to guide future treatment decisions.

By making the trial results public, efforts to develop precision cancer treatments – based on individual genomic profiles – could be accelerated.

"We in the Netherlands feel that we should make ourselves ready for precision medicine, to ensure we utilize the opportunities of precision medicine to the max. We need to identify all types of potential targets in tumors – not only the common tumor types, but also the very rare tumors, and then try to match those cancers with existing drugs. You can also identify opportunities for clinical trials, and investigational drug compounds that are under development."

"Our centralized testing is done by the Hartwig Medical Foundation, a nonprofit foundation, that facilitated the whole genome sequencing and created this database that is publicly available. Without this type of philanthropy, and help from other societies and foundations, this initiative would not be what it is now," concludes Voest.

Reference: D.L. van der Velden, et al. (2019) The Drug Rediscovery protocol facilitates the expanded use of existing anticancer drugs. Nature. DOI: 10.1038/s41586-019-1600-x 

Emile Voest, PhD, was speaking to Laura Elizabeth Lansdowne, Science Writer for Technology Networks.

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Laura Elizabeth Lansdowne
Laura Elizabeth Lansdowne
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