Italy has become the first European country to provide national healthcare access to a new therapeutic combination for approximately 800 patients each year diagnosed with metastatic colorectal cancer with BRAF mutations.
Italy is the first country in Europe to guarantee, through its national healthcare system, first-line access to a new therapeutic combination for patients with metastatic colorectal cancer with a BRAF mutation – one of the most aggressive forms of the disease. The therapy has been shown to double survival rates compared to standard treatments. The combination of two targeted molecular drugs, encorafenib and cetuximab, along with traditional chemotherapy, has transitioned from being a “last resort” to a first-choice treatment. Approximately 800 people will benefit each year, representing 8-10% of patients with metastatic disease carrying the BRAF mutation, within a cancer that diagnoses roughly 48,000 new cases annually in Italy.
Doubling Life Expectancy (and Exceeding 30 Months)
“The decision by AIFA [Italian Medicines Agency] is based on data from the randomized phase three BREAKWATER study, which evaluated the association of chemotherapy with encorafenib and cetuximab compared to the standard of care in patients with metastatic colorectal cancer with BRAF (V600E) mutation,” explains Fortunato Ciardiello, one of the study’s authors and a professor of medical oncology at the University of Campania Luigi Vanvitelli in Naples.
The results, published in the New England Journal of Medicine, demonstrate that the new combination doubles overall patient survival, increasing it from a median of approximately 15–16 months to over 30 months. “This treatment represents a turning point for a population of patients who, until a few years ago, had very limited therapeutic options and extremely rapid disease progression,” Ciardiello emphasizes. “Historically, about half of these patients did not even receive a second line of treatment. The employ of targeted molecular therapy only in advanced stages did not allow for recovery of the clinical benefit observed in studies. But, the early introduction of targeted molecular therapy, in association with chemotherapy, radically changes the clinical course of the disease, making it more controllable and doubling life expectancy.”
Testing for the Mutation Should Be Done Early
For all patients, knowing whether their tumor has a specific genetic mutation can develop a significant difference. This information is often used to guide treatment decisions, with oncologists choosing a drug or combination of medications based on the so-called “molecular profile” of the neoplasm. However, necessary tests to identify potential mutated genes are not always performed, both because they are not always reimbursed by the national healthcare system and because sophisticated equipment is needed to perform these analyses.
“Identifying the BRAF mutation from the time of metastatic disease diagnosis allows for immediate orientation of the therapeutic choice towards the most effective option,” stresses Stefania Napolitano, an oncology researcher at the University of Campania Luigi Vanvitelli. “That is, having access to a therapy that has demonstrated the greatest benefit when used as a first-line treatment. Colorectal cancer should 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 doubles survival.” The true innovation introduced in Italy is first-line access to this treatment. “If the new treatment is used only after the failure of standard therapies, the benefit is largely lost,” Napolitano specifies. “It is intervening immediately, at the beginning of metastatic disease, that the maximum result is obtained.”
Law 648/96 Avoids Delays, Valuable for Patients
In the United States, based on the results of the BREAKWATER study, this approach has already been implemented in clinical practice since last year. “As the Oncological Group of Southern Italy, we contributed to accelerating Italy’s access to this therapeutic opportunity,” concludes Roberto Bordonaro, president of GOIM and director of the Oncology Department and Complex Structure of Medical Oncology at Garibaldi Hospital in Catania. “The procedure provided for by Law 648/96 demonstrates that the National Health Service has tools to make innovative therapies available when there is robust scientific evidence and a high clinical need, avoiding delays that, in such an advanced stage of the disease, can directly impact survival. In this case, it has done so for one of the most aggressive forms of colorectal cancer, a type of cancer that now affects men and women in almost equal measure and whose incidence is increasing in the under-50 population. GOIM thus confirms its commitment to translating scientific evidence into concrete benefits for cancer patients, actively contributing to reducing therapeutic inequalities and improving standards of care.”
