Crossing the Valley of Death with Advanced Therapy

Crossing the Valley of Death with Advanced Therapy.

Is there hope for patients with advanced cancer?

Yes there is.

Yet, experimental treatments raise controversy. Although it seems obvious that new technologies are needed to supplement existing ones to help patients with currently incurable cancer, the Valley of Death, the gap between the laboratory and clinic, claims most projects. Unfortunately, crossing the Valley is not getting easier. Instead, it is more and more difficult every year to convert promising medical technologies into clinical trials. The one constant in biomedicine seems to be that regulation can only increase, leading to continuous increase in costs.

Experimental cancer therapy can mean many things, but usually it refers to a technology whose safety and efficacy has (not yet) been proven in rigorous clinical trials. Sometimes the situation can be that the drug has been used for some other patient population. Some drugs or treatment approaches never found a sponsor and thus there was no money for clinical trials, which cost millions. In fact, the current average cost of developing a new cancer drug has been calculated to be about 5 billion USD. The continuous increase in development costs is reflected in the price of drugs which have skyrocketed.

There are two basic approaches that can be employed in experimental therapy. When experimental therapy is administered according to a rigid protocol defined in advance the approach is called a clinical trial. There is always a chance of therapeutic benefit in clinical trials, because otherwise the trial would not be acceptable ethically. However, in fact the primary goal of a trial is to increase scientific information while patient benefit is a secondary goal. Clinical trials are the main mechanism by which clinical medicine improves and thus they are of critical importance for humankind including future patients and their close ones.

Experimental therapy can also be given in an individually tailored manner without a strict protocol, and in this scenario the only purpose is to try to help the patient. In fact, the aim of the intervention separates clinical trials from experimental treatment most clearly; is the primary goal to increase scientific knowledge or to help an individual?

Experimental therapy is based on science and it should be distinguished from “alternative therapy” which means therapy not based on science.

It can be easily be overlooked that most “routine” treatment is also experimental on the patient level. For example, if there is a “treatment A“, which is based on rigorous scientific evidence, it usually means that hundreds or thousands of patients were treated in clinical trials in comparison to “treatment B”. Perhaps A was effective in 60% and B in 45%. Thus A became the “standard therapy” used for all patients, even though 40% did not benefit from it, and in fact some patients who received A without effect might have benefited from B.

In the case of metastatic cancer, the most depressing aspect of routine therapy is not the fact that it may have low efficacy, or that it can cause severe side effects. Instead, the worst part is that it is well known what it can do at its best. With several exceptions, including many blood cancers, a proportion of pediatric cancers and certain rare adult solid tumors, cancer which has spread beyond local areas cannot be cured with routine treatments. This news usually comes as a shock to patients and their relatives.

Is there any hope?

Yes!

Many new types of treatment are entering clinical practice. As described in my book “Crossing the Valley of Death with Advanced Therapy”, cancer immunotherapy is one of the most promising. After more than 100 years of development many immunotherapeutics have entered late stage clinical testing and a few have already entered routine use. In contrast to most other classes of cancer drugs, immunotherapy appears to have curative potential even in the setting of metastatic cancer. However, currently only a minority of patients benefit and thus much work remains.

Unfortunately, the obstacles in the path of implementing scientific discovery for the benefit of patients continue getting more and more difficult. Nowhere is this more evident than in the story of the Advanced Therapy Access program. Utilizing the EU Advanced Therapy directive, and its “Hospital Exemption”, 290 patients with incurable cancer were treated with oncolytic adenoviruses, a potent form of immunotherapy. Although the treatment program can be considered a clinical success, a new department head of Finnish regulatory agency FIMEA asked the police to investigate if the individualized treatment program was in fact not a clinical trial done without a trial permit.  The book tells the story and also reviews the history of oncology, immunotherapy, gene therapy and oncolytic viruses.

Akseli Hemminki, MD, PhD

professor of oncology, scientist, enterpreneurer

Crossing the Valley of Death with Advanced Therapy. Published by Nomerta, Turku, Finland, 2015. Available at http://www.nomerta.net and several e-book stores globally