ANNETTE LEXA , PhD in Toxicology
MARCH 8, 2016
A priori, if we believe official messages communicated through the national cancer plan 2014-2019 (1) , we are witnessing real progress in the domain of anti-cancer therapies, and society (via patient associations) is ready to make it possible for everyone - in the name of the sacrosanct "equality of opportunity" - to have access to the best treatments, especially experimental ones. Otherwise, society and patient associations will even consider that this would be a "loss of opportunity".
Faced with the boom in oral chemotherapy, the 2014-2019 national cancer plan - which is silent on the origin of this boom - gives great importance (much more than to prevention) to improving "compliance (adherence to treatment) and management of adverse events" of new "innovative" anti-cancer therapies.
The term "compliance" (page 16 of the report) is scary and says a lot about the managerial necessity to make them accepted at all costs to the body and psyche of reticent patients by "securing" their care "pathway".
For the past 10-15 years, we have been witnessing an almost frenetic rush to bring new anti-cancer molecules to market. At the same time, the price of these new molecules is exploding. Patients are almost constrained to be enrolled in therapeutic trials.
What patients don't know is that there is no correlation between price, cost to market and efficacy in terms of survival rates. Moreover, these new molecules are not subject to rigorous clinical trials or to the search for proof of efficacy. Their efficacy - if it exists - is purely statistical and it is the standardization of treatments that prevails by type of cancer and not by type of patient. A careful reading of the scientific articles published on this subject in recent years even suggests that it is more important to put them on the market than to ensure their effectiveness and safety (3).
These drugs benefit from a fast-track marketing procedure. However, it has been proven that these drugs placed on the market prematurely have more serious adverse effects than those placed on the market more rigorously. Worse, once a molecule is placed on the market (such as bevacizumab), it is difficult to withdraw it from the market.
In the United States, of the 71 compounds approved by the FDA (Food and Drug Administration) between 2002 and 2014, the improvement in survival for all cancers combined is 2 months (5). For solid tumors, a review by the EMA (European Medicines Agency) shows an improvement of 1.5 months (3).
Currently, in Europe and in the USA, the regulatory agencies accept non-randomized trials, trials without controls, biased protocols, phase III trials when phase II was not convincing and they turn a blind eye to the quality of publications of these trials.
Worse, they accept as proof of "efficacy" new "innovative" molecules, "surrogate end points", measurements of biochemical sub-parameters, which are less costly to implement and which replace the only criterion that should prevail in oncology, survival, as a criterion of efficacy. It doesn't matter if you die in 10 days, the oncologist will look with satisfaction at your biomarkers rising.
The sky is getting a little darker when we learn (9) that a serious setback is announced in the new health law in the USA (21st Century Cures Act) whose stated objective is to make the best possible return on investment by reducing the time and number of patients in clinical trials, or even to abolish all clinical trials and replace them with "surrogate end points" (biochemical sub-parameters), in vitro and in silico studies. The USA is paving the way for a regression that is all the more serious since currently, in the USA, one third of drugs are approved after trials lasting less than 6 months and the average number of patients is 760. Underhanded negotiations around the future transatlantic treaty make this scenario increasingly likely as far as we are concerned.
In the USA, a number of oncology experts even believe that the moral red line between reasonable profits and profits has been crossed (3, 6). Partly because the poorest cannot afford to pay, as they no longer have medical insurance (a cancer treatment costs the insured about 20,000 to 30,000 dollars).
In France, costs are the same but we don't realize it because we are all covered by health insurance and optimal reimbursement.
In terms of "fight against cancer", it is also important to remember that 85% of the research is public and therefore financed by taxpayers and donations, the oligopolistic market (which relates to the oligopoly, a market characterized by a small number of sellers against a large number of buyers) of these pharmaceutical companies spending only 1.5% of its revenues on this research, between 5 to 13% on clinical trials and between 20 to 45% on marketing.
After this little clarification, we have a very different reading of the latest 2014-2019 cancer plan: the explosion of patient recruitment in early phase clinical trials of "innovative" drugs (do they really have a choice?), the public financial participation in this forced march, which is duly praised, leaves a strange bitter taste: is it the health of patients or the market that takes precedence? Not only are patients being lied to, but it is seriously damaging to both patients and research. For their safety alone, patients and physicians must demand greater rigour. Balanced health care budgets are also at stake.
Finally, it is questionable whether health agencies are serving the interests of patients or laboratories: in light of the appointment of Professor Agnès Buzyn as head of the Haute Autorité de Santé, it is reasonable to wonder (7, 8). Health agencies should regain their primary vocation, which is to ensure the protection of the public, and they should provide clear and transparent information to the public.
REFERENCES
1. Plan Cancer 2014-2019 , LE RAPPORT AU PRÉSIDENT DE LA RÉPUBLIQUE , Février 2016
2. Au nom de tous les seins, documentaire France 5
3. Light D.W., Lexchin J., Editorials, Why do cancer drugs get such an easy ride? Rushed approvals result in a poor deal for both patients and cancer research , BMJ 2015;350:h2068
4. Prasad V et coll., The Strength of Association Between Surrogate End Points and Survival in Oncology: A Systematic Review of Trial-Level Meta-analyses. JAMA Intern Med. 2015 Aug;175(8):1389-98
5.Fojo T, Mailankody S, Lo A. Unintended consequences of expensive cancer therapeutics
- the pursuit of marginal indications and a me-too mentality that stifles innovation and
creativity, JAMA Otolaryngol Head Neck Surg 2014;140:1225-36.
6. Hagop Kantarjian et coll., High Cancer Drug Prices in the United States: Reasons and Proposed Solutions J Oncol Pract 2014 Jul 6;10(4):e208-11.
7. Les petits arrangements de la nouvelle présidente de la Haute autorité de santé (7 mars 2016) https://www.mediapart.fr/journal/france/070316/les-petits-arrangements-de-la-nouvelle-presidente-de-la-haute-autorite-de-sante
8. Le professeur Agnès Buzyn nommée Directeur de la HAS. La victoire de big onco (8 mars 2016) http://docteurdu16.blogspot.fr/2016/03/le-professeur-agnes-buzyn-nommee.html 9. Avorn J and Kesselheim A.S., The 21st Century Cures Act — Will It Take Us Back in Time? N Engl J Med 2015; 372:2473-2475