Expanded analyses from AEGEAN trial

Prof Mariana Brandão, medical oncologist at Institut Jules Bordet and Prof Martin Reck, pulmonologist at the German Center for Lung Research, discussed the expanded analysis of the AEGEAN trial, evaluating associations of ctDNA clearance during neoadjuvant therapy with pCR and EFS in patients with resectable NSCLC.

The AEGEAN trial tested perioperative immunotherapy with durvalumab alongside chemotherapy, starting with neoadjuvant therapy, followed by surgery, and continuing with one year of adjuvant durvalumab. Compared to neoadjuvant chemotherapy alone, this approach significantly improved both EFS and pCR. A key takeaway from the trial is the importance of achieving pCR, as it strongly predicts long-term outcomes. Patients with pCR have a much lower risk of relapse, while those without pCR face a higher relapse risk. This has led to investigating early markers, such as ctDNA, to predict pCR. Using advanced sequencing techniques, the AEGEAN trial monitored ctDNA clearance to correlate with tumour response and survival outcomes.

The expanded analysis of 283 biomarker-evaluable patients revealed three major findings. First, patients who were ctDNA-positive at baseline and achieved pCR had early ctDNA clearance, detectable within the first two cycles of neoadjuvant therapy. Second, those who did not clear ctDNA early were unlikely to achieve pCR. Finally, ctDNA clearance was more likely in patients treated with durvalumab compared to placebo, and this also translated into improved EFS.

These results pave the way for future personalised treatments. Patients who fail to achieve ctDNA clearance may need intensified treatment with targeted therapies, bispecific antibodies, or novel agents. The study raises important questions about optimising adjuvant therapy, as current treatment with adjuvant durvalumab may not be enough for all patients. The use of ctDNA as an early biomarker could help tailor treatment strategies, identifying patients who might benefit from additional interventions.