The availability in Argentina of a new drug, encorafenib, expands the therapeutic options for the treatment of two types of cancer in advanced stages that present a genetic alteration of the BRAF gene.
The new drug is a targeted therapy that, in two different combinations with other medications also selective or personalizeddemonstrated benefits in the treatment of metastatic stage colorectal cancer (colon and rectum) and unresectable or metastatic melanoma.
Encorafenib, presented by Pfizer, inhibits the action of a pathway (called MAPK), responsible for stimulating the growth and proliferation of tumor cells. Always in those cases in which the presence of the BRAF mutation is verified. Encorafenib is administered as second-line therapy for the treatment of metastatic colorectal cancer in combination with cetuximab, a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), a protein that is found to be altered in malignant cells, favoring their growth. and multiplication.
In cases of unresectable or metastatic melanomathe indication is from the first line of treatment together with binimetinib, a medication that inhibits the activity of proteins (MEK1 and MEK2) that are altered and that favor the multiplication process of cancer cells. Both encorafenib and binimetinib are administered orally, while cetuximab is administered intravenously.
The era of personalized medicine
“We are witnessing a stage of the personalized medicine, in the search for the best treatment for the right patient and the availability of this combination is a clear example of advances in this specific area of patients with metastatic colorectal cancer with BRAF V600E mutation. Until now, in Argentina we did not have a specific treatment scheme for this subtype of tumor”, stated Dr. Juan Manuel O’Connor, medical oncologist, Head of the Gastrointestinal Tumors Unit of the Alexander Fleming Private Institute of Oncology.
“He colon cancer In our country it is a serious health problem. It constitutes the second cause in incidence and mortality within the different tumors, which is why they are frequent pictures in the oncologist’s office. In this sense, being able to count on new therapeutic options and directed by biomarkers, as in this case, allows for a greater probability of response and greater clinical benefit for the patient”, concluded Dr. O’Connor.
New drug for colorectal cancer and melanoma
The approval granted by the ANMAT for the combined use of encorafenib + cetuximab for the treatment of BRAF V600E mutation-positive metastatic colorectal cancer was based on results from the BEACON CRC clinical study, which demonstrated that this combination resulted in a 10-fold higher objective response rate (20% vs. 2 %) to that achieved with standard medication; overall survival (OS) was also higher: 8.4 months versus 5.4 months in the control group, and the median progression-free survival (SPL) achieved was 4.2 months versus 1.5 months.
The objective response rate shows the reduction of both the number and the size of the metastases, it is an iindisputable indicator of treatment efficacy, while the median progression-free survival, as its name indicates, indicates the time that is achieved without the disease progressing. Lastly, overall survival marks the average life extended by the use of medication, including mortality from any cause(8). The combination of encorafenib with cetuximab was superior to standard treatment in all these variables analyzed.
Colon and rectal cancer: the second most frequent Argentina
According to figures from National Cancer Institute Based on projections from the Global Cancer Observatory (GLOBOCAN 2020), almost 16 thousand cases of colorectal cancer (CRC) are diagnosed in our country per year, which makes it the most frequent type of tumor after breast cancer and therefore over those of the lung, prostate and kidney, representing 12.1% of the total cases. In addition, more than 7,000 people die each year from this type of tumor in our country, according to the latest vital statistics report (DEIS 2020) from the National Ministry of Health.
Son risk factor’s to develop colorectal cancer, among others, those related to lifestyle, such as a sedentary lifestyle, poor diet, overweight and obesity, excessive alcohol consumption and smoking. So is having a personal or family history of colorectal cancer or colorectal polyps and inflammatory bowel disease (such as Crohn’s disease or ulcerative colitis).
Yes ok many people do not experience symptoms In the early stages of the disease, changes in bowel movements, presence of bleeding in feces, abdominal pain and sudden weight loss, among others, warrant immediate consultation with a specialist. If routine studies are performed, such as colonoscopy or fecal occult blood test, can be detected early or even prevented. In general, it is recommended to do it from 45 years of age. CRC can affect both men and women(14) and, in the vast majority of cases, it occurs without any history in the family.
In Dr. O’Connor’s opinion “the colon cancer It is a preventable disease and we can reduce its mortality. It is important to take this into account and go to the doctor to carry out the corresponding studies. On the other hand, innovation and better knowledge of the biology of the disease allow us to improve treatment options as in the case of patients with this BRAF V600E mutation.”
Colon and rectal cancer is the second most frequent in Argentina, behind breast cancer
Approval in melanoma
Regarding the approval of the combination of encorafenib and binimetinib for the treatment of adult patients with unresectable or metastatic melanoma with the BRAF V600 mutation was supported by the COLUMBUS study, published in The Lancet, a randomized, open-label, phase 3 trial.
The investigation showed that the new combination orbhad a significant improvement in median PFS and overall survival compared to the drug vemurafenib, reaching a median PFS of 14.9 months compared to 7.3 months in the control group, and a median overall survival of 33.6 months, which doubles the overall survival evidenced in the control group (16.9 months)16. Until now, no combination has demonstrated a median overall survival of greater than 25 months, so the new combination treatment has the potential to become a new standard of care for patients with this mutation.
“The advances achieved in recent years in the advanced melanoma treatment are very important, both in terms of molecular targets and immunotherapy. We have managed to control this disease for years in a growing percentage of cases, but we know that at the moment more than half of the patients will end up dying from this cause. Having new treatment options that can exceed the efficacy and/or improve the tolerance of already established treatments is always welcome,” said Dr. Gabriela Cinat, medical oncologist, Head of the Melanoma and Sarcoma Functional Unit of the Institute of Oncology ‘Ángel H. Roffo’ from the University of Buenos Aires
“This combination has clearly demonstrated its efficacy in this scenario and, although it is not compared head-to-head with the other two previously approved that act through a very similar mechanism of action, we could say that its efficacy is at least similar. Its toxicity profile would appear to be generally more tolerable than the others, especially in terms of flu-like symptoms or skin reactions,” Dr. Cinat reported. “All of these advances were achieved through research – both basic and clinical – in a collaborative way,” she added.
Melanoma: which conditions increase the risk of developing it
The main conditions that increase the risk of developing melanoma are exposure excessive sunlight, age, family history and smoking. Among others, they also stand out for having a large number of moles and being very white-skinned, with freckles, blonde or red hair, and light-colored eyes.
Currently, both combinations, both for metastatic colorectal cancer and for advanced melanoma, in addition to the approval of the ANMAT, They are approved and available in the United States, Europe, Latin America, and many other countries around the world.
