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

• Manuel Valladares Ayerbes ^[1] ; Maria José Safont ^[2] ; Encarnación González Flores ^[3] ; Pilar García Alfonso ^[4] ; Enrique Aranda ^[5] ; Ana Maria López Muñoz ^[6] ; Esther Falcó Ferrer ^[7] ; Luís Cirera Nogueras ^[15] ; Nuria Rodríguez Salas ^[8] ; Jorge Aparicio ^[16] ; Marta Llanos Muñoz ^[9] ; Paola Patricia Pimentel Cáceres ^[17] ; Oscar Alfredo Castillo Trujillo ^[10] ; Rosario Vidal Tocino ^[11] ; Mercedes Salgado Fernández ^[12] ; Antonieta Salud Salvia ^[13] ; Bartomeu Massuti Sureda ^[18] ; Rocio Garcia Carbonero ^[14] ; Maria Ángeles Vicente Conesa ^[19] ; Ariadna Lloansí Vila ^[20]
  1. [1] Hospital Universitario Virgen del Rocío

     Hospital Universitario Virgen del Rocío

     Sevilla, España

     
  2. [2] Hospital General Universitario de Valencia

     Hospital General Universitario de Valencia

     Valencia, España

     
  3. [3] Hospital Universitario Virgen de las Nieves

     Hospital Universitario Virgen de las Nieves

     Granada, España

     
  4. [4] Hospital General Universitario Gregorio Marañón

     Hospital General Universitario Gregorio Marañón

     Madrid, España

     
  5. [5] Hospital Universitario Reina Sofia

     Hospital Universitario Reina Sofia

     Cordoba, España

     
  6. [6] Complejo Asistencial Universitario de Burgos

     Complejo Asistencial Universitario de Burgos

     Burgos, España

     
  7. [7] Hospital Son Llàtzer

     Hospital Son Llàtzer

     Palma de Mallorca, España

     
  8. [8] Hospital Universitario La Paz

     Hospital Universitario La Paz

     Madrid, España

     
  9. [9] Hospital Universitario de Canarias

     Hospital Universitario de Canarias

     San Cristóbal de La Laguna, España

     
  10. [10] Hospital Universitario Central de Asturias

      Hospital Universitario Central de Asturias

      Oviedo, España

      
  11. [11] Hospital Universitario de Salamanca

      Hospital Universitario de Salamanca

      Salamanca, España

      
  12. [12] Complexo Hospitalario Universitario de Ourense

      Complexo Hospitalario Universitario de Ourense

      Ourense, España

      
  13. [13] Hospital Universitario Arnau de Vilanova

      Hospital Universitario Arnau de Vilanova

      Lérida, España

      
  14. [14] Hospital Universitario 12 de Octubre

      Hospital Universitario 12 de Octubre

      Madrid, España

      
  15. [15] Hospital Universitari Mutua de Terrassa, Terrassa, Spain
  16. [16] Hospital Universitari i Politècnic La Fe, Valencia, Spain
  17. [17] Complejo Hospitalario Area II de Cartagena Hospital Universitario Santa Lucia, Cartagena, Spain
  18. [18] Hospital Universitario de Alicante, Alicante, Spain
  19. [19] Hospital General Universitario José Maria Morales Meseguer, Murcia, Spain
  20. [20] AMGEN S.A., Barcelona, Spain

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 26, Nº. 10, 2024, págs. 2640-2651
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • 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.