ASCO 2023 | FIRE-4: influence of baseline liquid biopsy results in 1L efficacy of FOLFIRI/cetux in RAS-WT mCRC

Sebastian Stintzing, MD, Charite University Hospital, Berlin, Germany, provides an overview of the liquid biopsy translational program of Phase III FIRE-4 (NCT02934529) trial evaluating the influence of baseline liquid biopsy results in first-line treatment efficacy of FOLFIRI/cetuximab in patients with tissue RAS-wild type (WT) metastatic colorectal cancer (mCRC). This randomized study tested the efficacy of early switch maintenance during first-line therapy (part 1) and re-challenge with cetuximab (part 2) in later-line treatment. In art 1, patients received FOLFIRI plus cetuximab until progression or intolerable toxicity (arm A) or FOLFIRI plus cetuximab followed by maintenance therapy with 5-FU/FA plus bevacizumab (arm B). Liquid biopsies were taken to analyze RAS and BRAF mutations. Among the 540 patients with evaluable baseline liquid biopsies, 13% had RAS mutations and 7% had BRAFV600E mutations. Patients with RAS mutations had significantly shorter progression-free survival (PFS) and overall survival (OS) compared to RAS wild-type patients. While no significant difference was observed in RAS wild-type patients between the two arms, RAS mutant patients showed a trend towards shorter survival in the standard arm. Liquid biopsy proved useful in detecting RAS mutations and verifying mutational status. This interview took place at the American Society of Clinical Oncology (ASCO) 2023 Annual Congress in Chicago, IL.

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