Randomized phase II trial of FOLFIRI-panitumumab compared with FOLFIRI alone in patients with RAS wild-type circulating tumor DNA metastatic colorectal cancer beyond progression to first-line FOLFOX-panitumumab: the BEYOND study (GEMCAD 17-01)

• Jorge Aparicio ^[4] ; Anna C. Virgili Manrique ^[1] ; Jaume Capdevila ^[5] ; Félix Muñoz Boza ^[2] ; Patricia Galván ^[3] ; Paula Richart ^[4] ; Helena Oliveres ^[3] ; David Páez ^[1] ; Jorge Hernando ^[5] ; Sara Serrano ^[2] ; Ruth Vera ^[6] ; Xavier Hernandez-Yagüe ^[7] ; Rafael Álvarez Gallego ^[8] ; M. Carmen Riesco-Martinez ^[9] ; Xavier García de Albeniz ^[10] ; Joan Maurel ^[3]
  1. [1] Hospital de la Santa Creu i Sant Pau

     Hospital de la Santa Creu i Sant Pau

     Barcelona, España

     
  2. [2] Hospital Universitari Sant Joan de Reus

     Hospital Universitari Sant Joan de Reus

     Reus, España

     
  3. [3] Hospital Clinic Barcelona

     Hospital Clinic Barcelona

     Barcelona, España

     
  4. [4] Departamento de Oncología Médica, Hospital Universitari i Politècnic La Fe, Avda. Abril Martorell 106, 46026, Valencia, España
  5. [5] Departamento de Oncología Médica, Hospital Universitario Vall d’Hebron, Vall Hebron Instituto de Oncología (VHIO), Barcelona, España
  6. [6] Departamento de Oncología Médica, Complejo Hospitalario de Navarra, Pamplona, España
  7. [7] Departamento de Oncología Médica, Institut Catalá Oncologia ICO, Girona, Girona, España
  8. [8] Departamento de Oncología Médica, Hospital Madrid Norte San Chinarro-Centro Integral Oncológico Clara Campal, Madrid, España
  9. [9] Departamento de Oncología Médica, Hospital Universitario 12 Octubre, Madrid, España
  10. [10] RTI Health Solutions, Barcelona, España

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 24, Nº. 11 (November), 2022, págs. 2155-2165
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Purpose Panitumumab plus FOLFOX (P-FOLFOX) is standard first-line treatment for RAS wild-type (WT) metastatic colorectal cancer. The value of panitumumab rechallenge is currently unknown. We assessed addition of panitumumab to FOLFIRI (P-FOLFIRI) beyond progression to P-FOLFOX in patients with no RAS mutations in liquid biopsy (LB).

    Methods In this randomized phase II trial, patients were assigned (3:2 ratio) to second-line P-FOLFIRI (arm A) or FOLFIRI alone (arm B). LB for circulating tumor DNA analysis was collected at study entry and at disease progression. Primary endpoint was 6-month progression-free survival. Two-stage Simon design required 85 patients to be included (EudraCT 2017-004519-38).

    Results Between February 2019 and November 2020, 49 patients were screened (16 RAS mutations in LB detected) and 31 included (18 assigned to arm A and 13 to arm B). The study was prematurely closed due to inadequate recruitment. Serious adverse events were more frequent in arm A (44% vs. 23%). Overall response rate was 33% (arm A) vs. 7.7% (arm B). Six-month progression-free survival rate was 66.7% (arm A) and 38.5% (arm B). Median progression-free survival was 11.0 months (arm A) and 4.0 months (arm B) (hazard ratio, 0.58). At disease progression, RAS or BRAF mutations in LB were found in 4/11 patients (36%) in arm A and 2/10 (20%) in arm B.

    Conclusions The BEYOND study suggests a meaningful benefit of P-FOLFIRI beyond progression to P-FOLFOX in metastatic colorectal cancer patients with WT RAS status selected by LB. This strategy deserves further investigation.