New precision medicine drugs improve colorectal cancer treatment

Three precision medicine drugs have been shown to be safe and effective in the treatment of metastatic colorectal tumors, according to three international studies led by the Vall d’Hebron Institute of Oncology (VHIO) presented at the European Society of Cancer Congress. and published in Natural medicine.

These are molecules that target very specific and specific mutations of three types of colorectal cancer. The work also identifies the optimal time to administer these drugs to a patient and in combination with what type of chemotherapy. These results, although preliminary, open the door to the possibility of incorporating these targeted therapies for patients who to date have a poor prognosis.

The most common tumor

Colorectal cancer is the most common tumor in men and women. Although it tends to appear primarily after the age of 50, in recent decades its frequency in younger people has increased significantly, leading to new lines of research focused on analyzing the role of environmental factors, to which we are exposed, intestinal microbiota and habits in the most frequent development of this disease.

Routine screening tests and early detection of colorectal tumors from the age of 50 favor their diagnosis in earlier phases, when the survival rate is 91% after five years. However, when they are detected in more advanced or metastatic phases, survival drops to 17%.

Towards precision medicine

For some time, precision medicine strategies have been used to treat metastatic colorectal tumors: a genomic profile of the tumor is obtained to identify which oncogenes are altered and will contribute to promoting tumor proliferation as cancer cells spread throughout the body and cause metastases.

In this sense, the first of the studies carried out by the VHIO focused on tumors that present the BRAF V600E mutation, “famous” because it is the one that the singer Pau Donnes had and affects between 10 and 12% of colorectal cancer patients. They are usually tumors with a very poor prognosis because they develop resistance to treatment very quickly.

A 2019 VHIO study showed that the administration of molecules that inhibit two oncogenes, BRAF and EGFR, achieved greater survival in these patients compared to standard chemotherapy therapy. This led to the approval of these two molecules and their use as second- and third-line treatment – in more advanced stages of the disease – in most countries.

The results are encouraging, especially when compared to chemotherapy as first-line treatment for these patients.”



Elena Elez

What the VHIO researchers have done in this new study is to evaluate the administration of these drugs together with first-line chemotherapy and conclude that this strategy improves the overall survival of patients.

“The results are encouraging, especially compared to the historical results of chemotherapy as a first-line treatment for these patients,” says Elez, who explains that they will now conduct a phase III study with a larger number of patients.

Researcher and oncologist Elena Elez, co-author of the three papers presented at ESMO.

VHIO

In the second of the works they present, they focus on molecules that inhibit angiogenesis, the ability of tumors to generate new blood vessels to provide themselves with oxygen and nutrients and thus be able to multiply and spread throughout the body . In recent years, drugs have been administered that block this ability of the tumor; one of them is fruquintinib.

In the study, which included nearly 700 patients with metastatic colon cancer who had not responded to standard chemotherapy treatment, researchers found that this drug was well tolerated and increased patient survival.

“It could potentially become a drug that we can prescribe to patients,” Elez said, noting that “today we only have two approved drugs with limited efficacy.”

HER2, mutation also in colon

Finally, VHIO researchers have focused on tumors with mutations in the HER2 protein commonly associated with breast cancer. In 2011, a study identified for the first time that between 4 and 7% of metastatic colorectal tumors also have this mutation, allowing the use of different therapeutic strategies directed against HER2. In this new work, “we applied as a first treatment option a tyrosine kinase inhibitor that induces the death of cancer cells driven by HER2 and a monoclonal antibody that binds to the HER2 protein and prevents the division and proliferation of tumor cells,” Elez explains.

In a group of 116 patients with HER2-overexpressing metastatic colorectal tumors who were refractory to chemotherapy and a monoclonal antibody, they found that when the inhibitor molecule and the monoclonal antibody were combined, 38.1% of patients responded to treatment at 12 months. compared with up to 3.3% doing so with monotherapy. With combined treatment, the overall survival of patients exceeds two years.

“The sooner these targeted therapies are included in the treatment of patients, the more effective they will certainly be,” the oncologist estimates.

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