Recent findings consolidate the role of liquid biopsy in the field, but prospective research is needed
Management of advanced solid tumours has been a major challenge due to the limited therapeutic strategies available in the past - mainly chemotherapy and radiotherapy. The advent of personalised medicine including targeted treatments has significantly improved the outcome of patients harbouring targetable molecular alterations, as well as the use of immune-checkpoint inhibitors (ICIs), alone or in combination with cytotoxic agents, for patients who cannot benefit from a targeted treatment.
Currently, the administration of ICIs is submitted to the immunohistochemical or immunocytochemical evaluation of PD-L1 expression level on tissue specimens (histological or cytological). However, the limited amount of tissue specimens and the necessity to apply less invasive sampling approaches has made necessary the adoption of liquid biopsy in patients treated with ICIs, as reported from some abstracts presented at the ESMO Immuno-Oncology Congress 2024.
In a poster presentation, the attention was on the role of blood DNA methylation profiles, performed with Infinium Methylation EPICv2.0 microarrays, of patients with advanced stage non-small cell lung cancer (NSCLC) and treated with ICIs (Abstract 24P). The authors highlighted that the blood methylation profile of patients with NSCLC was stable between baseline and follow up, supporting the hypothesis that blood DNA methylation profile may be a stabile biomarker not influenced by therapy.
A second study tried to identify circulating biomarkers which may be useful to perform patient selection and stratification in advanced stage NSCLC (Abstract 28P). The findings demonstrated an increase of somatic mutation rate and of neutrophil to lymphocyte ratio (NLR) values at the time of progression of disease in patients with NSCLC who have received an ICI-based treatment.
The prognostic role of liquid biopsy was also explored in other studies discussed in Geneva. In a poster presentation analysing the role of circulating tumour DNA (ctDNA) in metastatic uveal melanoma, the authors showed that ctDNA levels have a significant predictive value for progression free survival and overall survival in this metastatic setting, treated with first or subsequent lines of therapy (Abstract 25P).
In another abstract, researchers tried to overcome the limitation of tissue-based combined positive score (CPS) to predict ICIs response in recurrent and/or metastatic squamous cell carcinoma of the head and neck (Abstract 27P). Results suggest that the analysis of peripheral immune cell populations may serve as a predictive biomarker for PD-1 inhibitor efficacy in this patient group.
Another crucial issue of the use of liquid biopsy in immuno-oncology is related to immune-related adverse events (irAEs) in patients receiving ICIs. This represents a major concern for cancer patients treated with ICIs mainly due to the absence of reliable predictive biomarkers. In a pivotal study also presented at the congress, it was suggested that changes in the relative balance of neutrophils and specific CD4+ T cell subpopulations were linked with an irAE (Abstract 37P). This evidence marks a first step toward identifying biomarkers that anticipate the onset of an irAE and consequently reduce the need for immunosuppressive treatment that could compromise the efficacy of ICIs.
Taken together, these data contribute to consolidate the role of liquid biopsy in ICIs administration. However, prospective clinical trials in the field are strongly welcomed.
