Kerstin Noëlle Vokinger: ‘New cancer therapies are being approved for patient groups not included in clinical trials’

The fight against cancer is one of the greatest battles in the history of medicine. The battle starts in basic research laboratories, continues with clinical trials in hospitals, and ends with the complex process of turning a scientific breakthrough into a commercial product. New treatments are enthusiastically welcomed by patients and doctors, and notable advances have been made, such as the revolutionary CAR-T treatments.

But expectations are not always met. Less than half of new cancer therapies increase survival rate, and many patients suffer from the drug’s high toxicity without obtaining any clinical benefit. What’s more, pharmaceutical companies have a policy of making cancer treatments three times as expensive as therapy for other diseases, and this is jeopardizing the sustainability of health systems.

Barcelona recently hosted the European Society of Medical Oncology (ESMO) Congress. At this event, in addition to the many announcements of new milestones in the fight against cancer, there were also research presentations into the problems associated with the current system of drug development and marketing. Kerstin Noëlle Vokinger, a 36-year-old doctor, lawyer and professor at the University of Zurich, presented on Monday the first findings of a novel investigation — pending publication in a prestigious scientific journal — carried out by researchers from her center, the Yale School of Medicine and the Harvard Medicine School. This study focuses on the differences between the patient profiles included in clinical trials and the patients who end up receiving the treatments.

Question. Why did you decide to do this work?

Answer. We had conducted other studies focused on cancer treatments: their clinical value, the pricing policies of pharmaceutical companies... So, we wanted to investigate whether the approval of new therapies by organizations such as the European Medicines Agency [EMA] or the United States agency [FDA] is aligned with clinical trials. That is, whether the profile of the patients included in the trials corresponds to the profiles of the patients who will later receive the treatments in the real world, as authorized by the agencies.

Q. And what have you discovered?

A. The results have surprised us. Obviously, we expected some differences. The patients in trials cannot always be totally representative of those in the real world. But we did not expect to discover that one in three oncology drugs approved in the United States and one in five in Europe are then administered to patients with profiles not included in the trials.

Q. How did you measure this?

A. We compared the trial population with the label population that appears on the drug once it has been approved. We did this based on the following criteria: age, disease subtype (e.g., certain mutation), disease severity (e.g., metastasis) and prior therapy.

Q. The FDA is less strict than the EMA on this point, correct?

A. We analyzed 89 drugs in 92 indications and, yes, in the United States this occurs more frequently. There it occurs in 32.9% of indications, a percentage that is 20.3% in the European Union and 22.7% in Switzerland. This can be risky for patients.

Q. Why?

A. Because problems of lack of efficacy and safety can arise. We do not know how these drugs work in some patients, simply because they have not been tested before in patients with their characteristics. Therefore, it is impossible to predict whether the results of the trials will be achieved with these patients. We must not forget, in addition, that many oncology drugs have serious adverse effects.

Q. In other words, there is a lack of evidence in some cases?

A. Absolutely. And we have to be careful at this time, when it is increasingly common for new cancer therapies to be approved by the accelerated route. That is, also with weaker evidence that must be confirmed later.

Q. That’s doubly problematic, right?

A. Yes. The sum of drugs approved with less evidence and their use in patient profiles not included in trials opens a scenario with a double risk: that the desired efficacy results are not achieved and that serious adverse effects arise.

Q. Why is this happening? Is it due to the eagerness to get new therapies to patients as quickly as possible? Or is it because of industry pressure?

A. This is a key question. We do not know enough about the decision-making processes of the EMA and the FDA to understand if there is, for example, pressure from the pharmaceutical industry or other stakeholders. The desire to speed up the approval of drugs to patients is also to be expected, but the truth is that we do not know very well. It is something that needs to be investigated further.

Q. After being put on the market, drugs are still subject to strict control by the so-called pharmacovigilance and those approved by the accelerated route must confirm the initial results. Does this not guarantee their safety and efficacy?

A. This phase is crucial. But then we see that often the studies that should provide this data are delayed for years or even never carried out.

Q. Is there a possibility that all this is discriminatory for some population groups? For example, it is often said is that women, or some ethnic groups, are less represented in trials than they should be…

A. Yes, it is, and it is a problem on which there are already published studies. We have an open investigation that tries to delve deeper into this in relation to age and gender. And our preliminary results show that, indeed, the profile of patients in the trials differs from those in the real world.

Q. You presented an advance of your findings at ESMO on Monday, while waiting for the full research to be published in a scientific journal, so you are focusing your presentation on oncological therapies. Have you found any differences with respect to other diseases?

A. Yes, we have differentiated between drugs for cancer and for other diseases. And although some differences can be seen, the trends remain.

Q. How can we ensure that drug trials and real-world use are more aligned?

A. I think there are many ways. The first, obviously, is to strive to ensure that the patients included in the trials reflect the patients in the real world as best as possible. Another would be for agencies to be aware of the problem that these findings reveal. In addition, society, doctors and patients must be better informed.

Q. How?

A. Misalignments between both patient groups should be outlined in the label. If a drug has not been tested in trials on patients with the characteristics of the patient, the doctor and the patient must know this. Then they can make one decision or another, with more or less risk, but they have the right to know.

Q. How does this affect public health funding for new therapies?

A. Obviously, it is essential. It is reasonable for health systems to want to consider whether they should fund these treatments, which are particularly expensive, in populations in which they have not been tested and, therefore, with very little evidence.