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

Jacopo Venturini1, Mehmet A Baysal1, Abhijit Chakraborty1

  • 1Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

NPJ Precision Oncology
|April 10, 2026
PubMed

Insights

Genomic instability from DNA damage response (DDR) alterations may predict better outcomes with immuno-oncology (IO) therapy. Absence of liver metastases and IO treatment independently predicted longer survival in patients with DDR alterations.

Area of Science:

  • Oncology
  • Genetics
  • Immunotherapy

Background:

  • DNA repair deficiencies lead to genomic instability.
  • Genomic instability is linked to patient response to immuno-oncology (IO) therapies.

Purpose of the Study:

  • To analyze the outcomes of patients in the IMPACT2 study based on DNA damage response (DDR) alterations and treatment type.
  • To determine the role of DDR alterations as biomarkers for IO therapy response.

Main Methods:

  • Retrospective analysis of 662 patients from the IMPACT2 study.
  • Stratification of patients based on the presence of DDR alterations (DDR altered vs. DDR wild-type).
  • Analysis of overall survival (OS) in relation to treatment type (IO, chemotherapy, anti-DDR agents) and clinical factors.

Main Results:

  • 109 patients (16.5%) had DDR alterations, and 553 (83.5%) were DDR wild-type.
  • In patients with DDR alterations, absence of liver metastases and IO therapy predicted longer OS.
  • In DDR wild-type patients, IO therapy, absence of liver metastases, and normal albumin/lactate dehydrogenase levels predicted longer OS.

Conclusions:

  • DDR alterations may be associated with improved outcomes in patients receiving IO therapy.
  • Absence of liver metastases is a significant predictor of longer OS across both DDR-altered and DDR wild-type cohorts.
  • Further prospective studies are needed to confirm the utility of DDR alterations as biomarkers for predicting IO response.

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