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Background <p>Efficacy of 2nd line treatment in advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma remains limited with no identified strong predictor of treatment efficacy. We evaluated the prognostic value of circulating tumor DNA (ctDNA) in predicting the efficacy of immune checkpoint inhibitors (ICI) plus chemotherapy in the randomized PRODIGE 59-FFCD 1707-DURIGAST trial.</p> Methods <p>ctDNA was evaluated before treatment (baseline) and at 4 weeks (before the third cycle of treatment, C3) using droplet-digital PCR assays based on the detection of CpG methylation.</p> Results <p>Progression-free survival (PFS) and overall survival (OS) were shorter in patients with a high (&gt;1.1 ng/mL) versus low (&lt;1.1 ng/mL) ctDNA concentration at baseline (2.3 vs. 5.8 months; HR = 2.19; 95% CI, 1.09–4.41; <i>p</i> = 0.03 and 4.5 vs. 12.9 months; HR = 2.73; 95% CI, 1.29–5.75; <i>p</i> &lt; 0.01), respectively, after adjustment for identified prognostic variables. Patients with a ctDNA decrease ≤75% between baseline and C3 versus a ctDNA decrease &gt;75% had a worse objective response rate (<i>p</i> = 0.007), shorter PFS (2.2 vs. 7.4 months, HR = 1.90; 95% CI, 1.03–3.51; p = 0.04) and OS (6.6 vs 16.0 months; HR = 2.18; 95% CI, 1.09–4.37; <i>p</i> = 0.03).</p> Conclusions <p>An early decrease in ctDNA concentration is a strong predictor of the therapeutic efficacy of ICI plus chemotherapy in advanced gastric/GEJ adenocarcinoma.</p> <p><b>Clinical Trial Information</b> NCT03959293 (DURIGAST).</p>

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Circulating tumor DNA strongly predicts efficacy of chemotherapy plus immune checkpoint inhibitors in patients with advanced gastro-esophageal adenocarcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月24日

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  • David Tougeron,
  • Christophe Louvet,
  • Jérôme Desramé,
  • Ludovic Evesque,
  • Antoine Angelergues,
  • Aurélien Carnot,
  • Gilles Breysacher,
  • Aziz Zaanan,
  • Nicolas Etchepare,
  • May Mabro,
  • Laure Kaluzinski,
  • Caroline Petorin,
  • Benoist Chibaudel,
  • Thomas Aparicio,
  • Anaïs Bodere,
  • Yves Rinaldi,
  • Karine Le Malicot,
  • Jean-François Emile,
  • Côme Lepage,
  • Aurélia Baures,
  • Hanane Djamai,
  • Valérie Taly,
  • Pierre Laurent-Puig

摘要

Background

Efficacy of 2nd line treatment in advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma remains limited with no identified strong predictor of treatment efficacy. We evaluated the prognostic value of circulating tumor DNA (ctDNA) in predicting the efficacy of immune checkpoint inhibitors (ICI) plus chemotherapy in the randomized PRODIGE 59-FFCD 1707-DURIGAST trial.

Methods

ctDNA was evaluated before treatment (baseline) and at 4 weeks (before the third cycle of treatment, C3) using droplet-digital PCR assays based on the detection of CpG methylation.

Results

Progression-free survival (PFS) and overall survival (OS) were shorter in patients with a high (>1.1 ng/mL) versus low (<1.1 ng/mL) ctDNA concentration at baseline (2.3 vs. 5.8 months; HR = 2.19; 95% CI, 1.09–4.41; p = 0.03 and 4.5 vs. 12.9 months; HR = 2.73; 95% CI, 1.29–5.75; p < 0.01), respectively, after adjustment for identified prognostic variables. Patients with a ctDNA decrease ≤75% between baseline and C3 versus a ctDNA decrease >75% had a worse objective response rate (p = 0.007), shorter PFS (2.2 vs. 7.4 months, HR = 1.90; 95% CI, 1.03–3.51; p = 0.04) and OS (6.6 vs 16.0 months; HR = 2.18; 95% CI, 1.09–4.37; p = 0.03).

Conclusions

An early decrease in ctDNA concentration is a strong predictor of the therapeutic efficacy of ICI plus chemotherapy in advanced gastric/GEJ adenocarcinoma.

Clinical Trial Information NCT03959293 (DURIGAST).