ADAURA TRIAL

The ADAURA trial, which investigated adjuvant osimertinib for patients with resected stage I to III non-small cell lung cancer (NSCLC) with classic EGFR mutations, has provided significant insights into the use of circulating tumour DNA (ctDNA) as a biomarker. The trial’s overall survival data, presented last year, showed clear benefits of three years of adjuvant osimertinib. However, questions remained about how to best tailor this treatment to individual patients, considering both its toxicity and cost.

The latest ctDNA analysis from the ADAURA trial, presented at ASCO this year, offers promising findings. Among patients with positive ctDNA at baseline, five were in the osimertinib arm and 13 in the placebo arm. In the osimertinib arm, four out of five patients showed ctDNA clearance, indicating a potential reduction or elimination of micrometastatic disease. In contrast, none of the patients in the placebo arm showed ctDNA clearance, suggesting persistent micrometastatic disease.

The ctDNA assay used in the trial was tumour-based and personalised, utilising whole exome sequencing. This method is more complex and not yet practical for routine clinical use. Patients who developed minimal residual disease (MRD) positivity during treatment had a high likelihood of disease relapse, with a median lead time of five months between MRD positivity and a detectable relapse on CT scans. Monitoring was more frequent for ctDNA (every three months) than for CT scans (every six months), which could influence relapse detection timing.

In the osimertinib arm, 60% of patients who developed ctDNA positivity or disease relapse did so after completing the three-year treatment. This indicates that osimertinib may have been controlling micrometastatic disease, which resurged once treatment stopped.

These findings suggest that ctDNA monitoring could potentially guide the duration of osimertinib treatment. For instance, some patients might benefit from extended treatment beyond three years, while others might safely stop earlier and be monitored closely for MRD. The ongoing TARGET trial is exploring these possibilities further.

In summary, while ctDNA analysis from the ADAURA trial is not yet ready for routine clinical application, it shows promise as a tool to tailor adjuvant osimertinib treatment more precisely, potentially reducing unnecessary exposure to the drug’s toxicity and improving patient quality of life. Future clinical trials will be essential to validate these findings and develop practical guidelines for ctDNA use in managing NSCLC.