FDA's Approval of Braftovi-Erbitux Combination Presents 'A Small Step Forward' for Patients with Metastatic Colorectal Cancer

The Food and Drug Administration’s (FDA) approval of Braftovi (encorafenib) and Erbitux (cetuximab) with or without Mektovi (binimetinib) for adults with metastatic colorectal cancer (CRC) with a BRAF V600E mutation is a welcomed approval, according to Dr. Richard Goldberg.

“It’s a welcome approval because patients with a BRAF V600E mutation have a poorer than average prognosis and more limited treatment options than other colorectal cancer patients. Having an effective, rationally designed regimen for them that attacks multiple points in the pathway that drives their tumor was sorely needed,” Goldberg, director emeritus of West Virginia University Cancer Institute and professor emeritus at West Virginia University, said in an interview with CURE®. “We were all excited to see how this works in our patients and to have it available as an FDA-approved regimen.”

The agency based its decision on results from the randomized, active-controlled, open-label, multicenter phase 3 BEACON CRC trial, designed to specifically study patients with previously treated metastatic CRC with a BRAF V600E mutation.

The combination improved overall survival (8.4 months versus 5.4 months), overall response rate (20% versus 2%) and median progression-free survival (4.2 months versus 1.5 months), compared with the control arm.

Goldberg noted that physicians will still use standard chemotherapy treatments as the first line of treatment for these patients, likely starting with a 5-fluorouracil-based regimen combined with a second chemotherapy drug; either irinotecan or Eloxatin (oxaliplatin) administered with the targeted agent Avastin (bevacizumab).

However, Goldberg said there has been evidence that suggests BRAF V600E mutated colon cancers show resistance to EGFR inhibitors Erbitux or Vectibix (panitumumab) as single agents. But, administering Erbitux together with Braftovi and Mektovi (binimetinib) increases the effectiveness.

“This is a way of adding to the number of drugs option that we have available for this subset of patients who have poor prognosis and fewer treatment options,” he explained.

Quality of Life

Oncologists and patients can decide whether to use Erbitux plus Braftovi with or without Mektovi, Goldberg said. The results with two drugs were nearly as good as those observed with three drugs giving patients and their doctors two options to consider. While the therapy is not curative, Goldberg noted, data from the BEACON study demonstrated it extended both survival and the maintenance of patients’ quality of life.

A Step Forward

The combination will become the preferred second-line treatment option, according to Goldberg. The hope is that it will help people maintain their quality of life and extend survival.

“This is a step forward; it’s not a giant step, but it’s a small step forward,” he said. “The other thing that’s important about this is that it shows that by using two targeted agents, you can interfere with a pathway that has been turned on like a stuck accelerator, a tumor promoter gene, in a more effective way that you can with just using a single drug in that pathway.”

In that instance, he explained, it is a new idea that turned out to be successful.

Even though colon cancers may look the same under the microscope, they are driven by different genomic abnormalities. As a result, physicians are having to subdivide management strategies for patients based on their genomic abnormalities.

This combination represents one of the early successes in that environment, which allows the cancer to thrive and take advantage of newer drugs that are being developed and can target those pathways in more than one place.

“As a model for treating colorectal cancer, and really many other cancers that are being understood to be more diverse than we had thought years ago, this is an important model,” he said. “I think future investigators are going to continue to use this strategy to combine targeted agents and I would hope we would get better at it with time.”

Read CURE®’s original coverage on the approval of Braftovi and Erbitux.