Combinational therapies, based on molecular and preclinical cancer research, are often seen as the future of cancer medicine: Cancer therapies are increasingly becoming combinations of two or even more drugs that reinforce each other and better keep the cancer under control. Separately, they may have no long-term effect, but together they can better keep the cancer under control and prolong lives. However, access to new combination therapies is highly unequal across and within European countries.
In order to map patient access to new combination therapies, the researchers surveyed 19 specialists working in 17 leading cancer institutes in nine European countries* about their experiences with 23 combination therapies for melanoma and lung cancer: Did they prescribe these combination therapies to their patients, and if so, was this in a clinical trial, in an early-access construct or as standard of care? And what, if any, were the stumbling blocks?
The study revealed that the routine practice of melanoma and lung cancer specialists differs across Europe, as the multi-colored table below shows. Differences in coverage were reported not only between countries, but also between hospitals and combinational therapies.
For example, the combination ‘Encorafenib + cetuximab’ for treating melanoma, was accessible and reported covered to patients in only three countries (Belgium, Czech Republic, and The Netherlands).
Reimbursed access was generally more prevalent for combinational therapies supported by clinical trials. ‘This could also explain the differences in access between melanoma and lung cancer that we saw,’ says Julie Vancoppenolle, first author of the study. ‘Our selected combination therapies for melanoma included EU-approved standard first-line combinations, whereas those for lung cancer included mostly unapproved second-line combinations.’
The overall cause of this variability, according to the researchers, is the huge complexity of the entire process of drug development, approval, pricing and reimbursement of these new combination therapies. ‘All chains in this process, from clinical trials to pricing negotiations, were developed for monotherapies,’ says research leader Wim van Harten. ‘But cancer research now suggests that combinational therapies should be seen as self-contained new therapies, rather than the sum of two independent drugs.’
- Clinical trials not always available and often small
Access to new combination therapies often depends on the availability of well-designed clinical studies. In some countries, no such clinical trials are carried out, so there will be no early access. Also, in precision medicine, patient populations are becoming increasingly specific and therefore small, which makes collecting sufficient evidence to convince healthcare authorities harder.
- Pricing negotiations more complex for combination therapies
Multiple producers are involved in the development of combination therapies, who have different interests and are competitors. This results in pricing negotiations that are even more complex and time-consuming than with monotherapies. Combinations are also used for ‘evergreening’ – renewing a patent on a drug for a new application. This, too, results in high prices.
‘As a result, we miss many opportunities in the development of new combination therapies,’ says Wim van Harten. ‘This development is so new, but at the same time so important for patients, that pharmaceutical companies also need to start thinking differently about their mutual relationship. In the future, most cancer treatments will be combination therapies so we all better invest in this.’
'Clinical trials, authorization processes and pricing can all be better aligned with new developments in cancer research, rather than lag behind,’ says Johan van de Gronden, director of the Dutch Cancer Foundation, which is a founding partner of the EFPN . ‘For example, the revision of the EU Pharma legislation offers a great opportunity to include combination therapies into the authorization process.’