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Purpose <p>Most patients with <i>BRAF</i>-mutant melanoma eventually develop resistance to BRAF/MEK inhibitors (BRAF/MEKi) and immune-checkpoint blockade. Emerging evidence from retrospective cohorts indicates promising activity from re-exposure to BRAF/MEKi after a treatment-free interval of targeted therapy (TT), probably due to tumor regression and proliferation of sensitive clones. However, there is limited prospective evidence on this approach.</p> Methods/patients <p>GEM1801 is a prospective observational study by the Spanish Melanoma Group (GEM), including 1123 patients treated at 37 centers. We conducted a descriptive analysis of baseline characteristics, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for the 24 patients who received a second course of BRAF/MEKi, either as retreatment (after relapse following prior adjuvant TT) or rechallenge (following prior progression on TT in the metastatic setting).</p> Results <p>Five patients underwent retreatment, and 19 received rechallenge. The BRAF/MEKi median free interval for retreatment was 20.9&#xa0;months (range 12.4–57.3), with an ORR of 20%, and median PFS and OS of 5.5 and 8.4&#xa0;months, respectively. The median free interval of TT for rechallenge was 6.8&#xa0;months, with an ORR of 31.6%, and median PFS and OS of 5.7 and 7.6&#xa0;months. Patients with ECOG ≤ 1 experienced longer survival with rechallenge (8.2 vs 4.3&#xa0;months; HR 9.07 [95% CI 1.37–59.8]; <i>p</i> = <i>0.022</i>).</p> Conclusion <p>Retreatment or rechallenge with BRAF/MEKi in the metastatic setting has shown clinical activity in patients with metastatic melanoma who lack therapeutic alternatives to prolong survival. Therefore, in our experience, it may represent a valid therapeutic strategy for selected patients.</p> Clinicaltrials.gov: NCT03605771 (registration date: 20-07-2018) <p>NCT03605771</p>

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Retreatment and rechallenge with BRAF/MEK inhibitors in patients with metastatic melanoma: results from the real-world Spanish Melanoma Registry (GEM-1801)

  • 期刊论文

  • 发表日期：

    2025年7月27日

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  • Pablo Ayala-de Miguel,
  • Eva Muñoz-Couselo,
  • Lourdes Gutiérrez-Sanz,
  • Luis Antonio Fernández,
  • Víctor Navarro-Pérez,
  • Miguel Ángel Berciano-Guerrero,
  • Francisco García-Arroyo,
  • Carlos Aguado-de la Rosa,
  • Pablo Cerezuela-Fuentes,
  • Margarita Majem,
  • Begoña Campos-Balea,
  • Ainara Soria,
  • Berta Hernández-Marín,
  • Almudena García-Castaño,
  • Salvador Martín-Algarra,
  • Iván Márquez-Rodas

摘要

Purpose

Most patients with BRAF-mutant melanoma eventually develop resistance to BRAF/MEK inhibitors (BRAF/MEKi) and immune-checkpoint blockade. Emerging evidence from retrospective cohorts indicates promising activity from re-exposure to BRAF/MEKi after a treatment-free interval of targeted therapy (TT), probably due to tumor regression and proliferation of sensitive clones. However, there is limited prospective evidence on this approach.

Methods/patients

GEM1801 is a prospective observational study by the Spanish Melanoma Group (GEM), including 1123 patients treated at 37 centers. We conducted a descriptive analysis of baseline characteristics, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for the 24 patients who received a second course of BRAF/MEKi, either as retreatment (after relapse following prior adjuvant TT) or rechallenge (following prior progression on TT in the metastatic setting).

Results

Five patients underwent retreatment, and 19 received rechallenge. The BRAF/MEKi median free interval for retreatment was 20.9 months (range 12.4–57.3), with an ORR of 20%, and median PFS and OS of 5.5 and 8.4 months, respectively. The median free interval of TT for rechallenge was 6.8 months, with an ORR of 31.6%, and median PFS and OS of 5.7 and 7.6 months. Patients with ECOG ≤ 1 experienced longer survival with rechallenge (8.2 vs 4.3 months; HR 9.07 [95% CI 1.37–59.8]; p = 0.022).

Conclusion

Retreatment or rechallenge with BRAF/MEKi in the metastatic setting has shown clinical activity in patients with metastatic melanoma who lack therapeutic alternatives to prolong survival. Therefore, in our experience, it may represent a valid therapeutic strategy for selected patients.

Clinicaltrials.gov: NCT03605771 (registration date: 20-07-2018)

NCT03605771