Triple Therapy in Metastatic CRC With BRAF Mutations: The New Standard of Care?

San Francisco – provided the first line treatment with targeted treatments in addition to chemotherapy, the benefits of a comprehensive response Braf Colon and transtebleptic colon and rectal transmitted v600E (MCRC), according to the experience of a broker of water.

The study was considered in Incuravinib (Braftovi) and Sittoxab (Eritox) as well as MFOLFOX6 (EC-FOLFOX6) against the care standard (SOC), and showed a total response rate of 60.9% with EC-Folfox6 compared to 40% with or without or without chemotherapy. Bevasizumab (Avastin), Scott Kubitz, PhD in Medicine, PhD, from the MD Anderson Cancer Center in Houston.

The average response duration was 13.9 months in the EC-Folfox6 arm and 11.1 months in the SuC arm, and the percentage of patients with a response that lasted for 6 months or 12 months was at least in the EC-Folfax6 arm more than twice that in the EC-Folfox6 arm. . The arm of the South Oil Company – 68.7% compared to 34.1%, and 22.4% compared to 11.1%, respectively, he said in a presentation at the conference. The American Association for Clinical Oncology Association (ASCO) on the cancers of the digestive system. The results were published simultaneously in Nature Medicine.

While the comprehensive survival data (OS) was not mature at the time of this analysis, there was a direction of the operating system preferred EC-Folfox6. In a medium follow-up of the operating system, it is 10.3 months in the EC-Folfox6 arm, 9.8 months in the SuC arm, the average operating system was not accessed in the EC-FOLFOX6 arm and 14.6 months in the SuC (risk ratio 0.47, 95% CI 0.318-0.691, P =0.00454). The operating system rates were 92.3%, compared to 87.1% in 6 months and 79.5%, compared to 66.1% in 12 months.

“This study supports EC and Folfox as a new standard for care in the first line of patients who suffer from Braf “Colon cancer and the microscopic metal cancer V600E” said Kubitz.

He also mentioned this Water The foundation results for The approval of the FDA in 2024 for the system To treat these patients, including in the first line position.

“There is definitely impressive improvement in response – basically 21 percentage points,” observer called Wales Missirmithm, PhD in Medicine, from the Cancer Center at the University of Colorado at Urara. We are all used to that Braf Since this treatment is very difficult, the group of patients is really aggressive, so these results, for me, change the practice. “

The results of the operating system are also “impressive, at least at first.”

Referring to a 41 -year -old patient Braf Fix the microscopic mismanage V600E, the stability of the microbiological satellites (PMMR/MSS) CRC, Missirmithth said that instead of waiting for a BRAF targeting treatment from the second or third line, “based on this summary … if you see one of these patients after that I will treat them yet A week using Enurvinib, Sitokimab and Volphox as the first font treatment. “

Braf V600E mutations occur in 8-12% of MCRCS cases, and it appeared as a distinct sub-type with a very bad diagnosis compared to wild type, as well as resistance to standard chemotherapy systems.

Kubitz pointed out that the data before the clinical showed that there is a benefit in combining the chemotherapy, Enurvinib, Sitokimab and the toxic chemotherapy of the cells, and that the use of Enurvinib was approved in addition to cytoximab in therapy. Braf V600E-Mutant CRC in the second and subsequent line settings based on the results of Lighthouse study.

“Despite this promising option for targeted treatments in the second and later line as shown in the Beacon study, the chemotherapy of the first line with or without a biological factor (for example, Bevasizumab) had a limited effectiveness Braf V600E-Mutant MCRC ”, Kubitz and colleagues wrote Nature Medicine.

“There are currently no treatments targeting the stimulation path in the first line of patients who suffer from Braf They added that “V600E-Mutant MCRC”, so “a treatment can show improved effectiveness in preparing the first line due to the bad diagnosis compared to Braf MCRC wild type.

Breakwater is an open -name and multi -centered study in the third stage that recorded patients who have not been treated before Braf V600E-MCRC transformed. Patients must have a measuring disease and MSS tumor. They were randomly chosen to one of three therapeutic arms:

• SOC: Choose the investigator for chemotherapy with or without Bevasizumab (n = 243)
• Triple combination: EC-Folfox6 (Issue = 236)
• Double composition: ancurghavinib in addition to cytoximab: (number = 158). The results of this group will be announced at a later time.

The average age of patients was 61 years old; 49.5% of them are female; About 60 % were eggs. About 37 % were Asian. ECOG 1 performance was seen at 42%; Most of them had tumors on the right side; It was 95.2 % PMMR / MSS.

The authors have reported that the events arising from TEAS occurred in 99.6% in the EC-Folfox 6 arm compared to 97.8% in the arm arm. The most common teaes was nausea (51.1 % compared to 48.2 %, respectively), anemia (36.4 % compared to 22.8 %), diarrhea (34.2 % compared to 46.9 %), decreased appetite (33.3 % compared to 25.0 %), vomiting (33.3 % For 21.1). %) The number of neutrophils (32.0%compared to 28.1%).

TEAES events of 3/4 degrees occurred in 74.0% of patients in the EC-Folfox 6 arm compared to 61.0% in the arm arm, while the events of AES associated with 3/4 degrees in 69.7% compared to 53.9% of patients, respectively. Kubitz indicated that there are no fifth -class Trases in the experimental arm.

“This encouraging data supports this system to become the new safety center in the country Braf V600E–MCRC transformed. The authors wrote: “Specifications are planned to perform pre -defined analyzes for mature survival free of progress and comprehensive survival data.”