The treatment of choice in patients with a so-called EGFR mutation in advanced (stage IV) non-small cell lung cancer consists of targeted treatment with a tyrosine kinase inhibitor. This type of drug is intended to inhibit the growth of the tumor. With these tablets, patients experience fewer side effects and a longer survival than with chemotherapy1. From Flaura trial2 previously reported that a new variant of this drug, osimertinib, would work better than the old variants gefitinib and erlotinib. Osimertinib is considerably more expensive, will be reimbursed in the Netherlands from 2020 and is now standard treatment3. In a recent Dutch study based on data from the NKR, the results of osimertinib were compared with the older and cheaper drugs. This study showed that the more expensive osimertinib only works better for a limited group of lung cancer patients than the standard tumor growth inhibitors.
Rolof Gijtenbeek, pulmonologist at the Medical Center Leeuwarden, and colleagues reported on this in the international journal The Lancet Regional Health Europe. The study involved a series of 1,109 patients treated between 2015 and 2020. It only looked at the standard EGFR mutations, Del19 and L858R.
Comparison of survival with different tumor growth inhibitors
The median overall survival for patients with a Del19 mutation was clearly better (28.4 months) than with an L858R mutation (17.7 months). The use of osimertinib increased strongly over time; from 3% in 2018 to 18% in 2019 and 94% in 2020. When comparing the median survival between the different tyrosine kinase inhibitors, the results of osimertinib (22.8 months) were not significantly better than those of gefitinib (19.7 months), erlotinib (23.2 months) and afatinib (23.3 months). Only in patients with a Del19 mutation and metastases in the brain did osimertinib prove better than the cheaper erlotinib.
Results of osimertinib in the Netherlands worse than in previous research
It was striking that the results of osimertinib in the Netherlands were worse than in the Flaura trial (where a survival of 38.6 months was reported).4). This can partly be explained by the inclusion of patients with advanced age or poor condition. Also, no difference in survival between the drugs could be demonstrated. A possible explanation is that with the cheaper drugs, in case of progression, i.e. the tumor growing or spreading, it is often still possible to switch to osimertinib. If the tumor grows or spreads while osimertinib is already being used, treatment options are limited. In the article in The Lancet Regional Health Europe, the researchers recommend repeating the study with longer follow-up. In addition, they indicate that research into the treatment policy for patients with an L858R mutation and metastases in the brain seems desirable.
Lidia Barberio, director of the Lung Cancer Netherlands patient association, says about the study:
As a patient organization, we believe it is important that research is carried out into the best application of the drug, even after a drug has come on the market. It is important for doctors and patients, especially for EGFR patients where different targeted therapies are available, to know in which case which agent is best to choose. We have a closed Facebook group for patients with the EGFR mutation where they can share experiences and knowledge with each other. Twice a year we also organize an information meeting for patients with lung cancer due to a so-called aberration, popularly referred to as a mutation.
Independent research is important and more expensive is not always better
‘The studies sponsored by the pharmaceutical industry often show good effects of expensive anti-cancer drugs. This independent study shows that it is important to take a good look at which cancer agent is most suitable for which lung cancer patient. We have now shown that the most expensive medicine is not always better and that is important knowledge to keep healthcare affordable and accessible to everyone,’ says Wouter van Geffen, pulmonologist Medical Center Leeuwarden.
https://www.longkankernederland.nl/longkanker/behandelingen/doelgerichte-therapie
https://www.nvmo.org/bom/osimertinib-als-eerstelijns-behandeling-voor-patienten-met-egfr-gemuteerd-niet-kleincellig-longcarcinoom/
https://www.zorginstituutnederland.nl/publicaties/adviezen/2020/09/21/pakketadvies-herbeoordeling-osimertinib-tagrisso
https://pubmed.ncbi.nlm.nih.gov/31751012/