Neo-DIANA: descriptive results of a prematurely terminated phase II trial of neoadjuvant atezolizumab, chemotherapy and bevacizumab in resectable EGFR-mutated NSCLC

Reducing postoperative recurrence remains an unmet need in locally advanced non-small-cell lung cancer (NSCLC), particularly in patients with epidermal growth factor receptor (EGFR)-mutated tumours, who are at higher risk of distant metastases after surgery; particularly brain metastases. Perioperative and neoadjuvant chemoimmunotherapy strategies have improved survival outcomes in unselected populations; however, the evidence in EGFR-mutated NSCLC remains limited because most pivotal trials - including NADIM, NADIM II, CheckMate 816, RATIONALE-315, CheckMate 77T and Neotorch - excluded patients with known EGFR mutations. This gap provides a rationale for exploring the use of anti-angiogenic agents combined with chemoimmunotherapy in a molecular subgroup that is usually less-immunoresponsive. While this strategy has demonstrated efficacy in the metastatic EGFR-mutated setting, as reported in IMpower150, ATTLAS/KCSG-LU19-04 or ORIENT-31 study, prospective evidence in resectable disease is lacking. The Neo-DIANA trial was a multicentre, open-label, non-randomised phase II clinical trial designed to investigate a neoadjuvant regimen combining atezolizumab, chemotherapy and bevacizumab, followed by surgery and adjuvant atezolizumab, in resectable stages IIIA and IIIB EGFR-mutated NSCLC. Because the trial was terminated early due to slow recruitment, no conclusions can be drawn regarding the efficacy of combination therapy in patients with resectable EGFR-mutated NSCLC. Further studies are still needed to explore perioperative strategies that may help reduce postoperative relapses in these patients.