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Sequential RAS mutations evaluation in cell-free DNA of patients with tissue RAS wild-type metastatic colorectal cancer: the PERSEIDA (Cohort 2) study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2024年4月20日

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  • Manuel Valladares-Ayerbes,
  • Maria José Safont,
  • Encarnación González Flores,
  • Pilar García-Alfonso,
  • Enrique Aranda,
  • Ana-Maria López Muñoz,
  • Esther Falcó Ferrer,
  • Luís Cirera Nogueras,
  • Nuria Rodríguez-Salas,
  • Jorge Aparicio,
  • Marta Llanos Muñoz,
  • Paola Patricia Pimentel Cáceres,
  • Oscar Alfredo Castillo Trujillo,
  • Rosario Vidal Tocino,
  • Mercedes Salgado Fernández,
  • Antonieta Salud-Salvia,
  • Bartomeu Massuti Sureda,
  • Rocio Garcia-Carbonero,
  • Maria Ángeles Vicente Conesa,
  • Ariadna Lloansí Vila

摘要

Purpose

RAS (KRAS/NRAS) mutational status on a tumor biopsy is mandatory to guide the best treatment in metastatic colorectal cancer (mCRC). Determining the RAS mutational status by tumor-tissue biopsy is essential in guiding the optimal treatment decision for mCRC. RAS mutations are negative predictive factors for the use of EGFR monoclonal antibodies. Cell-free DNA (cfDNA) analysis enables minimally invasive monitoring of tumor evolution.

Methods/patients

PERSEIDA was an observational, prospective study assessing cfDNA RAS, BRAF and EGFR mutations (using Idylla™) in first-line mCRC, RAS wild-type (baseline tumor-tissue biopsy) patients (cohort 2). Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression.

Results

117 patients were included (103 received panitumumab + chemotherapy as first-line treatment). At baseline, 7 (6.8%) patients had RAS mutations, 4 (3.9%) BRAF mutations and no EGFR mutations were detected (cfDNA, panitumumab + chemotherapy subpopulation [panitumumab + Ch]). The baseline RAS mutational status concordance between tissue and liquid biopsies was 94.0% (93.2%, panitumumab + Ch). At 20 weeks, only one patient in the study (included in the panitumumab + Ch) had an emerging cfDNA RAS mutation. No emerging BRAF or EGFR mutations were reported. At disease progression, 6 patients had emergent mutations not present at baseline (RAS conversion rate: 13.3% [6/45]; 15.0% [6/40], panitumumab + Ch).

Conclusions

The concordance rate between liquid and solid biopsies at baseline was very high, as previously reported, while our results suggest a considerable emergence of RAS mutations during disease progression. Thus, the dynamics of the genomic landscape in ctDNA may provide relevant information for the management of mCRC patients.