2023-06-26 08:18:44
ROS1 translocation is a rare form of lung cancer that is sensitive to treatment with a protein inhibitor. The study by Deirdre Hekkelman-ten Berge, research physician at the Erasmus Medical Center and radiologist at the Admiraal de Ruiter hospital, and colleagues investigated how often ROS1 occurs in the Netherlands, how it was treated and what the results were in practice. The two-year survival after treatment with protein inhibitors was 53%. Progression-free survival was only 8.6 months and was mainly limited by the occurrence of brain metastases. The researchers conclude that a brain scan should already be performed in this patient group at the time of diagnosis and that there is a need for new protein inhibitors that are also active in the brain.
In recent decades, variants of lung cancer caused by specific genetic abnormalities, for example EGFR, ALK and ROS1, have been discovered. Drugs have been developed that are specifically effective for the treatment of these disorders. ROS1 translocations are mainly seen in non-smoking, young patients with adenocarcinoma. That is a non-small cell tumor, often in the outer parts of the lung. The protein inhibitor crizotinib was approved by the European Medicines Agency (EMA) in 2016 for the treatment of patients with ROS1 lung cancer.
Disappointing progression-free survival due to metastases in the brain
A total of 67 patients were included in this study, representing 0.34% of patients with stage IV adenocarcinoma. This low number is mainly determined by the rarity, but also partly explained by the fact that not all patients are (or cannot be) tested for genetic abnormalities. It also explains why so little is known about it. Three-quarters of the patients received a so-called systemic treatment, which works throughout the body, mainly with crizotinib (n=34). The two-year survival after crizotinib use was 53%, with a median progression-free survival of 8.6 months. These results are disappointing compared to the results in the trials, but are comparable to outcomes from other real-world studies. An important limiting factor for survival was the presence or development of metastases in the brain.
Concentration of care and international cooperation required
During the study period, only 39% of patients had a brain scan before starting treatment. This has now been included as standard diagnostics in the ESMO guideline (Hendriks et al). Given the rare nature of ROS1 lung cancer, treatment in the Netherlands is concentrated in a limited number of centers of expertise. Research requires international cooperation and focuses, among other things, on the application of new medicines that are more effective in the brain.
Importance of cooperation and further research
Merel Hennink has been a ROS1+ patient since 2014, founder of the Merels World Foundation and patient advocate on a national and international level. She indicates: ‘With all the rare subgroups within lung cancer that can be treated thanks to research, it is becoming increasingly difficult to conduct individual research. Collaboration is crucial in this respect, preferably internationally. The wish of the foundation is to set up international networks. Networks in which researchers inform each other about what they are researching, in which hospitals can provide each other with study material and in which people with ROS1+ cancer can also assist each other and inform each other about new studies in which they may be able to participate. These would be good initiatives to improve the outcomes of people with ROS1+ cancer. What would certainly help in the Netherlands is to reimburse new drugs on the basis of realistic figures, so that patients with the right drugs can live longer in good health.’
Real-world treatment patterns and survival of patients with ROS1 rearranged stage IV non-squamous NSCLC in the Netherlands Deirdre ten Berge, Ronald Damhuis, Joachim Aerts, Anne-Marie Dingemans Lung Cancer 2023.
Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Hendriks et al,
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