The remaining challenges with neo-adjuvant immunotherapy in early-stage NSCLC

During ELCC 2024, Dr Kristof Cuppens, pulmonologist and thoracic oncologist at the Jessa Hospital in Hasselt, chaired a session discussing the remaining challenges surrounding the integration of immunotherapy in the (neo)-adjuvant treatment of patients with early-stage non-small cell lung cancer (NSCLC).

In recent years, several clinical trials have convincingly demonstrated the potential benefit of immune checkpoint inhibitors as part of the adjuvant, neo-adjuvant, or perioperative treatment for patients with early-stage NSCLC. However, while these data have generated lots of enthusiasm, they have also stirred up new debates.

First, the availability of more effective (neo)-adjuvant treatment strategies has reinvigorated discussions on the definition of resectability in NSCLC. In addition to a better identification of ‘resectable NSCLC patients’, the disease biology of the individual patient needs to be taken into consideration when making (neo)-adjuvant treatment decisions. For example, data suggest that patients with PD-L1 expression derive a more pronounced treatment effect from (neo-)adjuvant immune checkpoint inhibition. However, PD-L1 expression is far from ideal to steer our patient selection and there continues to be a burning need for better biomarkers. In this respect, promising results have emerged on the use of circulating tumour DNA.

Another important challenge with neo-adjuvant (chemo)-immunotherapy relates to discrepancies between conventional imaging and pathological analyses. In clinical practice, it is not rare that a patient with an apparent stable disease on imaging following neo-adjuvant immunotherapy in fact has a major or even complete response in his/her final pathological evaluation. In addition to this, pseudo-progression on neo-adjuvant therapy has been described and it continues to be challenging to distinguish these patients from patients with a true progression. To address this issue, there is a need for more accurate response evaluation tools.

Despite the remaining challenges and uncertainties, Dr Cuppens is convinced that immune checkpoint inhibitors will become an increasingly important part of the (neo)-adjuvant treatment for a large proportion of early-stage NSCLC patients in the years to come.