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Cancer

Circulating Tumor DNA Monitoring and Blood Tumor Mutational Burden in Solid Cancer Patients Treated with Atezolizumab

Strategic Insights

— 1 min read

Researchers at the Francis Crick Institute have published a new study on the relationship between circulating tumor DNA (ctDNA) and blood tumor mutational burden (bTMB) in patients with metastatic solid tumors treated with atezolizumab. The study found that molecular response (MR) to atezolizumab, measured by a 50% decrease in ctDNA tumor fraction (TF) at cycle 3 day 1, was associated with improved progression-free survival (PFS) and overall survival (OS) in patients with stable disease (SD).

Key Takeaways:

  • Molecular response (MR) to atezolizumab was associated with improved PFS (9.7 vs 1.5 months from C3D1; HR = 0.27) and OS (21.1 vs 14.3 months from C3D1; HR = 0.44) in patients with stable disease (SD).
  • bTMB was correlated with tissue-based TMB (tTMB) when TF was high ( = 1%), but not with OS in this cohort.
  • The study found that 61% of baseline samples had predicted clonal hematopoiesis (CH) variants, but no correlation between maximum variant allele frequency (maxVAF) of predicted CH and TF was seen.
  • Quantification of ctDNA enables therapy response monitoring and is critical for interpretation of bTMB as a proxy for tTMB.
  • The study included 153 patients treated with atezolizumab as part of the pan-tumor MyPathway study (NCT02091141).

Statistics:

  • 61% of baseline samples had predicted clonal hematopoiesis (CH) variants.
  • Maximum mutant allele frequency (maxVAF) of predicted CH variants was not correlated with ctDNA tumor fraction (TF).
  • Patients with molecular response (MR) to atezolizumab had improved PFS and OS compared to those without MR.

Sources:

  • "Circulating Tumor Dna Monitoring and Blood Tumor Mutational Burden In Patients With Metastatic Solid Tumors Treated With Atezolizumab." Molecular Oncology, 2025.
  • Francis Crick Institute, Canc Evolut & Genome Instabil Lab, London, United Kingdom (Citation: NewsRx. Findings on Solid Cancer Detailed by Investigators at Francis Crick Institute (Circulating Tumor Dna Monitoring and Blood Tumor Mutational Burden In Patients With Metastatic Solid Tumors Treated With Atezolizumab). Immunotherapy Weekly. June 25, 2025; p 1176.)

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