It is one of the “big-killers” for health, with over 48,000 new cases per year in Italy. Not only that, it is the leading cause of death associated with cancer in young people under 50. Finding new ways in the approach to colorectal cancer is therefore fundamental.
And there is no shortage of good news. Italy is the first country in Europe to guarantee, through the National Health Service, front-line access to a new therapeutic combination for patients with metastatic colorectal cancer with BRAF mutation, one of the most serious and unfortunate forms of the disease. A therapy that has been shown to double survival compared to standard. Not only that. Thanks to liquid biopsy, there is a possibility of cure even for patients with advanced colon cancer that no longer responds to standard therapies.
This is demonstrated by the results of a study, promoted by the Oncology Group of Southern Italy (GOIM) in which the European Institute of Oncology played a central role, just published in Annals of Oncology,
Treatments in Italy before in Europe
The important news is that the combination of two molecularly targeted drugs, encorafenib and cetuximab, associated with traditional chemotherapy, has become first choice therapy. Approximately 800 people will benefit from it in Italy every year, i.e. 8-10% of patients with metastatic disease who are carriers of the BRAF mutation, in the context of a tumor which in Italy records around 48 thousand new diagnoses every year.
While Europe is waiting for the formal green light from the EMA, on the initiative of the GOIM (Southern Italy Oncology Group), the Italian Medicines Agency (AIFA) has in fact shortened the timeframe, activating an early path to access the therapy through the procedure provided for by law 648/96. This tool allows innovative medicines to be made available before the conclusion of the European bureaucratic process when there is an urgent clinical need and overwhelming scientific evidence. The AIFA approval was communicated on the occasion of the GOIM congress in Bari.
“AIFA’s decision is based on data from the randomized phase III BREAKWATER study which evaluated the association of chemotherapy with encorafenib and cetuximab compared to standard of care in patients with metastatic colorectal cancer with BRAF (V600E) mutation”
explains Fortunato Ciardiello, one of the authors of the study as well as professor of medical oncology at the Luigi Vanvitelli University of Campania in Naples.
The results, which appeared in the New England Journal of Medicine, showed that with the new combination the overall survival of patients doubled, which thus went from a median of approximately 15–16 months to over 30.
“This treatment represents a turning point for a patient population that, until a few years ago, had very limited therapeutic options and extremely rapid disease progression. Historically, around half of these patients did not even receive a second line of treatment. The use of molecularly targeted therapy only in the advanced stages did not allow the clinical advantage observed in the studies to be recovered. While the early introduction of molecularly targeted therapy, in association with chemotherapy, radically changes the clinical history of the disease, making it more controllable and doubling life expectancy”
underlines Ciardiello.
It is important to recognize the characteristics of the tumor
Molecular characterization is fundamental from the moment of diagnosis of metastatic disease, because it allows timely access to a therapy that has been shown to offer the maximum benefit when used as a first-line treatment.
“Identifying this mutation right from the diagnosis of metastatic disease allows you to immediately orient the therapeutic choice towards the most effective option”
underlines Stefania Napolitano, medical oncology researcher at the Luigi Vanvitelli University of Campania in Naples.
Colorectal cancer can no longer be considered a single disease: there are biologically different subtypes that require different therapeutic strategies, and recognizing them promptly means offering people the most appropriate therapy at the right time. Precision medicine, in this case, is not a slogan but a concrete tool that allows you to double survival. The real innovation introduced first in Italy is therefore access to the front line.
“If the new treatment is used only after the failure of standard therapies, the benefit is largely lost. It is by intervening immediately, at the beginning of the metastatic disease, that the maximum result is achieved”
Napolitano specifies.
What liquid biopsy can tell
Thanks to liquid biopsy, there is a possibility of cure even for patients with advanced colon cancer that no longer responds to standard therapies. This is demonstrated by the results of a study, promoted by the same Southern Italy Oncology Group (GOIM) in which the European Institute of Oncology played a central role, published in Annals of Oncology.
The study, called CAVE-2 GOIM, was a multicenter trial that subjected 156 patients with colon cancer refractory to at least two lines of therapy to targeted treatment, based on the result of the liquid biopsy. The objective of the study was to define whether re-treatment with epidermal growth factor (EGFR) inhibitor drugs alone or in combination with immunotherapy could constitute a therapeutic option in a patient population with reduced chances of cure. The study demonstrated the importance of the liquid biopsy (i.e. on blood) which, compared to the “solid” one (i.e. on tumor tissue), which is initially carried out to make the diagnosis, is able to capture all the mutations and information on the tumor as it grows and spreads.
“After progression to the first and second line of therapy, the treatments available for advanced colorectal cancer are unfortunately less numerous and active. The typical case is represented by patients with tumors without RAS/BRAF mutations, for which the use of EGFR (Epidermal Growth Factor Receptor) inhibitor drugs is one of the most effective therapies, but only in the first line. In this scenario, the CAVE-2 GOIM study wanted to investigate whether, by further selecting this group of patients on the basis of the liquid biopsy, it was It is possible to find new, more targeted treatments. We therefore evaluated the potential role of retreatment with an anti-EGFR drug (Cetuximab), in association or not with an immunotherapy drug (Avelumab), in the subgroup of patients who did not present “resistance mutations” (the gene alterations that allow some tumors to resist molecularly targeted drugs) to Cetuximab on the liquid biopsy. We thus discovered that survival in these patients was significantly better than historical data for approved standard therapies. with great clinical benefit and a favorable tolerability profile”
explains Davide Ciardiello, doctor of the Division of Medical Oncology of Gastrointestinal and Neuroendocrine Tumors of the IEO, first author of the work.
