New triple targeted therapy: rewriting the treatment standard for advanced colorectal cancer?

New triple targeted therapy: rewriting the treatment standard for advanced colorectal cancer?. Colorectal cancer often has no obvious symptoms in the early stage, and many patients are already in the advanced stage when they are discovered. Dr. Michael Castro, an expert on digestive tumors from the Good Doctor Medical Network, pointed out that the average five-year survival rate for early-stage colorectal cancer is as high as 90%, while the advanced stage is less than 20%.

Nowadays, according to the patient’s gene mutations and their interactions, the comprehensive use of multiple therapies and the development of personalized and precise treatment plans have become a new direction in the treatment of advanced colorectal cancer.

Recently, a clinical study funded by the National Cancer Institute (NCI) found that:

Compared with the “irinotecan + cetuximab” dual therapy, the “irinotecan, cetuximab, verofenib” triple therapy can significantly prolong the tumor-free survival of patients with metastatic colon cancer. This discovery is expected to rewrite the standard treatment plan for colorectal cancer.

BRAF mutations occur in approximately 15% of patients with metastatic colorectal cancer. Among them, BRAF V600E mutation is the most common BRAF mutation. Colorectal cancer patients with this mutation usually do not respond well to treatment and have a poor prognosis.

Scott Kopetz, MD, MD Anderson Cancer Center is an oncologist researching BRAF mutations. He has previously led a variety of clinical studies of related combination therapies, including a blockbuster Phase III clinical trial (BEACON). The study found that: Cetuximab + Encorafenib (Encorafenib) combination therapy can significantly reduce tumors and prolong patient survival. This study was published in the New England Journal of Medicine last year. In April 2020, the FDA approved the combination therapy to treat patients with metastatic colorectal cancer with BRAF V600E mutation.

In this new study, the team of Dr. Kopetz hopes to find a more effective combination therapy. They included 106 patients with metastatic colorectal cancer, including the V600E mutation, all of whom had received chemotherapy and did not respond. These patients were randomly assigned to two groups, receiving irinotecan + cetuximab dual therapy, and irinotecan + cetuximab + Vemurafenib (Vemurafenib) triple therapy.

The results showed that patients who received triple therapy had a higher tumor response rate (17% VS 4%) and longer tumor-free survival.

Dr. Kopetz explained the mechanism of action of triple therapy from the molecular level:

Irinotecan is a cytotoxic chemotherapeutic drug that can kill cancer cells; Cetuximab is an anti-EGFR targeted drug that inhibits tumor growth by blocking the EGFR protein; Verofenib is an anti-BRAF Targeted drugs, by blocking BRAF protein, inhibit tumor growth. Triple therapy can better play a synergistic effect and block multiple pathways to inhibit tumor growth. In addition, it is more effective to add chemotherapeutics to treat metastatic colorectal cancer.

The researchers also found that in patients treated with triple therapy, the frequency of ctDNA (circulating tumor DNA) of the BRAF V600E mutant allele decreased by 87%; while in patients receiving dual therapy, ctDNA did not decrease.

“This shows that the detection of ctDNA by liquid biopsy is expected to be an effective method for evaluating short-term treatment response.”

(source:internet, reference only)

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