Companion Diagnostic for Encorafenib + Cetuximab in BRAF V600E alteration in mCRC Receives FDA Approval

Companion Diagnostic for Encorafenib + Cetuximab in BRAF V600E alteration in mCRC Receives FDA Approval

Source – Foundation Medicine

In order to identify patients with metastatic colorectal cancer (mCRC) who could be candidates to receive encorafenib (Braftovi) in conjunction with cetuximab (Erbitux), the FDA has authorized FoundationOne CDx for use as a companion diagnostic.

The qualitative in vitro test, which is based on next-generation sequencing, analyzes 324 genes using circulating cell-free DNA. The assay makes use of technology that enables it to recognise substitutions, insertions, and deletions in 311 different genes, including rearrangements in 8 genes and copy number variations in 3 genes.

After receiving previous treatment, the FDA authorized the use of encorafenib in conjunction with cetuximab in adult patients with mCRC with the BRAF V600E mutation. The decision was supported by data from the Phase III BEACON CRC trial (NCT02928224), in which encorafenib plus cetuximab resulted in a median overall survival (OS) of 8.4 months vs. 5.4 months with the control regimen of irinotecan or FOLFIRI plus cetuximab.

After receiving previous therapy, the regulatory body authorized a new indication for cetuximab in September 2021 for use in adult patients with mCRC and a BRAF V600E mutation. Once more, the choice was based on information from BEACON CRC. Additional information revealed that the doublet had an objective response rate (ORR) of 20% as opposed to the control regimen’s ORR of 2%. In the investigational and control groups, the median progression-free survival was 4.2 and 1.5 months, respectively.

“Companion diagnostics are high-quality, well-validated genomic tests that provide critical information to help oncologists make informed treatment decisions for our patients. This new companion diagnostic indication for FoundationOne Liquid CDx provides oncologists with an important, non-invasive genomic testing option for metastatic patients with this difficult-to-treat condition.”

Mia Levy, MD, PhD, chief medical officer at Foundation Medicine

FoundationOne CDx is intended to be leveraged to determine which patients may derive benefit from approved targeted therapies such as alectinib (Alecensa); EGFR inhibitors like erlotinib (Tarceva), osimertinib (Tagrisso), gefitinib (Iressa), afatinib (Gilotrif), dacomitinib (Vizimpro); mobocertinib (Excivity); capmatinib (Tabrecta); and entrectinib (Rozlyn Trek) in non-small cell lung cancer. Alpelisib (Piqray), rucaparib (Lynparza), entrectinib (Rubraca), and olaparib (Lynparza) are also authorized as companion diagnostics for prostate cancer, breast cancer, and solid tumors, respectively.

Patients with histologically or cytologically proven mCRC harboring a BRAF V600E mutation who progressed after one or two previous treatments were enrolled in the worldwide, multicenter, open-label, Phase III BEACON CRC study.

Encorafenib, binimetinib, and cetuximab were given to study participants (n = 665) in a 1:1:1 randomization. Other options included encorafenib plus cetuximab at the same doses and schedule plus irinotecan at 180 mg/m2 on days 1 and 15 or cetuximab at the same dose and schedule plus either irinotecan or cetuximab at the investigator’

Treatment continued up to the onset of a fatal illness, unacceptable toxicity, withdrawal of consent, start of alternative treatment, or withdrawal of consent altogether.

ECOG performance status (0 vs. 1), prior irinotecan use (yes vs. no), and cetuximab formulation (US licenced vs. European authorized) were the main stratification variables.

The study’s primary effectiveness metric was OS, while supplementary metrics were PFS, ORR, and the length of response by blinded independent central review.All of the participants that underwent randomization had their OS and PFS assessed. The first 220 patients who were randomly allocated to the doublet and control arms of the trial had their ORR and DOR evaluated.

216 patients in total had their safety assessed. Cetuximab was administered to these patients at a dosage of 400 mg/m2 initially, followed by a weekly dose of 250 mg/m2, along with 300 mg of encorafenib every day. Fatigue, diarrhea, nausea, dermatitis acneiform, stomach discomfort, decreased appetite, arthralgia, and rash were among the toxicities associated with the doublet that were most often reported.

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