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<p>Neoadjuvant immunotherapy can induce pathologic complete response (pCR) in patients with localized deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) tumors. The long-term outcomes of these patients are unknown, as is the clinical utility of measuring circulating tumor DNA (ctDNA). Follow-up was evaluated in patients enrolled in a phase II trial (NCT04082572) that evaluated the efficacy and safety of pembrolizumab in patients with localized dMMR/MSI-H tumors. The primary outcomes of this trial have previously been reported. 3-year EFS and OS rates were 80% (95% CI: 66% – 93%) and 94% (95% CI: 86% – 100%). Patients without detectable ctDNA after pembrolizumab had higher 3-year EFS and OS rates than patients with detectable ctDNA after pembrolizumab (3-year EFS 92% vs 20%; <i>p</i> &lt; 0.001, 3-year OS 100% vs 80%; <i>p</i> &lt; 0.001). Patients with colorectal cancer (CRC) who had undetectable ctDNA after pembrolizumab were more likely to have pCR compared to those with detectable ctDNA after pembrolizumab (91% vs 0%; <i>p</i> = 0.03). Patients with CRC who were managed non-operatively and had undetectable ctDNA after pembrolizumab had a higher 2-year EFS rate than patients with detectable ctDNA after pembrolizumab (100% vs 33%; <i>p</i> = 0.03). Pembrolizumab demonstrates long-term efficacy in patients with localized dMMR/MSI-H tumors.</p>

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Long-Term Efficacy of Pembrolizumab and the Clinical Utility of ctDNA in Locally Advanced dMMR/MSI-H Solid Tumors

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月15日

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  • Michael LaPelusa,
  • Wei Qiao,
  • Bryan Iorgulescu,
  • Francis San Lucas,
  • Keyur Patel,
  • Deepak Bhamidipati,
  • Jane Varkey Thomas,
  • Nancy You,
  • Wai Chin Foo,
  • Dipen Maru,
  • Selvi Thirumurthi,
  • Van Morris,
  • Scott Kopetz,
  • Michael Overman,
  • Kaysia Ludford

摘要

Neoadjuvant immunotherapy can induce pathologic complete response (pCR) in patients with localized deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) tumors. The long-term outcomes of these patients are unknown, as is the clinical utility of measuring circulating tumor DNA (ctDNA). Follow-up was evaluated in patients enrolled in a phase II trial (NCT04082572) that evaluated the efficacy and safety of pembrolizumab in patients with localized dMMR/MSI-H tumors. The primary outcomes of this trial have previously been reported. 3-year EFS and OS rates were 80% (95% CI: 66% – 93%) and 94% (95% CI: 86% – 100%). Patients without detectable ctDNA after pembrolizumab had higher 3-year EFS and OS rates than patients with detectable ctDNA after pembrolizumab (3-year EFS 92% vs 20%; p < 0.001, 3-year OS 100% vs 80%; p < 0.001). Patients with colorectal cancer (CRC) who had undetectable ctDNA after pembrolizumab were more likely to have pCR compared to those with detectable ctDNA after pembrolizumab (91% vs 0%; p = 0.03). Patients with CRC who were managed non-operatively and had undetectable ctDNA after pembrolizumab had a higher 2-year EFS rate than patients with detectable ctDNA after pembrolizumab (100% vs 33%; p = 0.03). Pembrolizumab demonstrates long-term efficacy in patients with localized dMMR/MSI-H tumors.