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<p>DNA repair deficiencies result in genomic instability. Data suggest that genomic instability is associated with response to immuno-oncology (IO) therapies. We analyzed outcomes of patients in the IMPACT2 study by the presence of DNA damage response (DDR) alterations and treatment type. Of 662 patients with ≥1 alterations: 109 (16.5%) had DDR alterations (treated, <i>N</i> = 85) and 553 (83.5%) were DDR wild-type (treated, <i>N</i> = 426). In patients with DDR alterations, absence of liver metastases (<i>p</i> = 0.029) and IO therapy (vs. chemotherapy, <i>p</i> = 0.020; vs. anti-DDR agents, <i>p</i> = 0.048) were independent factors predicting longer overall survival (OS). In the DDR-wild-type cohort, independent factors predicting longer OS were IO therapy (compared with each other treatment group: vs. IO+non-IO combinations, <i>p</i> = 0.003; vs. chemotherapy, <i>p</i> &lt; 0.001; vs. anti-DDR agents, <i>p</i> &lt; 0.001; vs. other targeted therapies, <i>p</i> = 0.006), absence of liver metastases (<i>p</i> &lt; 0.001), and normal albumin (<i>p</i> &lt; 0.001) and lactate dehydrogenase (<i>p</i> = 0.001) levels. Prospective studies are warranted to refine the role of DDR alterations as biomarkers of IO response.</p>

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Outcomes of patients with or without DNA repair pathway alterations: the MD Anderson IMPACT2 study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月10日

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  • Jacopo Venturini,
  • Mehmet A. Baysal,
  • Abhijit Chakraborty,
  • Timothy A. Yap,
  • Siqing Fu,
  • David S. Hong,
  • Sarina A. Piha-Paul,
  • Aung Naing,
  • Jordi Rodon Ahnert,
  • Ecaterina Elena Dumbrava,
  • Jennifer Beck,
  • Yang Liu,
  • Michael Kahle,
  • David J. Vining,
  • Funda Meric-Bernstam,
  • Apostolia Maria Tsimberidou

摘要

DNA repair deficiencies result in genomic instability. Data suggest that genomic instability is associated with response to immuno-oncology (IO) therapies. We analyzed outcomes of patients in the IMPACT2 study by the presence of DNA damage response (DDR) alterations and treatment type. Of 662 patients with ≥1 alterations: 109 (16.5%) had DDR alterations (treated, N = 85) and 553 (83.5%) were DDR wild-type (treated, N = 426). In patients with DDR alterations, absence of liver metastases (p = 0.029) and IO therapy (vs. chemotherapy, p = 0.020; vs. anti-DDR agents, p = 0.048) were independent factors predicting longer overall survival (OS). In the DDR-wild-type cohort, independent factors predicting longer OS were IO therapy (compared with each other treatment group: vs. IO+non-IO combinations, p = 0.003; vs. chemotherapy, p < 0.001; vs. anti-DDR agents, p < 0.001; vs. other targeted therapies, p = 0.006), absence of liver metastases (p < 0.001), and normal albumin (p < 0.001) and lactate dehydrogenase (p = 0.001) levels. Prospective studies are warranted to refine the role of DDR alterations as biomarkers of IO response.