Episode 7: AEGEAN study results confirm ctDNA as a predictive biomarker for pCR in NSCLC patients with neoadjuvant treatment

In this episode of WND, Professor Johan Vansteenkiste from University Hospitals Leuven and Professor Mariana Brandao, a medical oncologist at Institut Jules Bordet in Brussels, introduce the AEGEAN trial investigating biomarkers in the field of NSCLC.

Chemotherapy combined with immunotherapy yields superior results compared to chemotherapy alone in NSCLC patients. In the peri-operative setting this typically involves 3-4 cycles of chemotherapy plus immunotherapy followed by surgery, followed by one year of immunotherapy. Pathological complete response (pCR) is serving as a surrogate marker for post-surgery outcomes.

In the AEGEAN trial, stage II-IIIB NSCLC patients received durvalumab + chemotherapy versus placebo before surgery. The trial yielded positive results, with a HR of 0.68 for EFS. Furthermore, it revealed a strong negative correlation between ctDNA evolution and achieving pCR. Samples showing total ctDNA clearance had a 50% chance of achieving pCR. Thus, ctDNA levels demonstrate reasonable accuracy in predicting pCR after just one cycle of chemoimmunotherapy. Future trials will investigate whether this early-response biomarker also predicts key endpoints such as EFS and OS.

The experts engage in a detailed discussion regarding the clinical implications of these findings. An important question arises: should patients achieving pCR still undergo surgery, particularly if ctDNA proves to be a reliable predictor? Currently, only half of the patients with ctDNA clearance achieve pCR, indicating that surgery remains necessary for many. Conversely, patients without ctDNA clearance continue to receive standard treatment. Interim subanalyses from various studies suggest that patients with incomplete pCR may benefit from the addition of postoperative immunotherapy.

The AEGEAN trial has a notable limitation in its use of personalized ctDNA analysis rather than standard commercial kits used in clinics, potentially yielding differing results. Nevertheless, this trial contributes valuable insights into biomarkers in the perioperative setting, aiding in treatment escalation or de-escalation decisions.

These trial findings offer several options. Patients with complete ctDNA clearance may proceed with immunotherapy alone before surgery. Alternatively, those with poor ctDNA clearance could explore other treatments, like double immunotherapy used for metastatic cases. Continued scientific exploration will guide clinicians toward new approaches in clinical practice.