Combining the VIGex gene expression signature with circulating tumor DNA (ctDNA) analysis may improve response prediction to immunotherapy in patients with advanced solid tumors, according to a study published in JCO Precision Oncology. The research, co-authored by investigators from VHIO’s Cancer Genomics Group and Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch, highlights the potential of this combined approach in the clinical trial context.
Predictive Biomarkers for Immunotherapy Response
Immunotherapy, which boosts the immune system to fight cancer, has shown promise, but only a fraction of biomarker-selected patients benefit. Elena Garralda, Medical Oncologist at the Vall d’Hebron University Hospital (HUVH) and Director of VHIO’s UITM-CaixaResearch, noted, "Cancer immunotherapy fails to achieve clinical responses in all patients and does not yield benefit in the treatment of many tumor types. There is therefore an unmet clinical need to identify robust biomarkers predictive of response to immune-based treatments."
Ana Vivancos, Head of VHIO’s Cancer Genomics Group, added, "In this context, immune gene expression signatures are emerging as potential biomarkers of response for immunotherapy. At VHIO, we have developed the VIGex gene expression signature as a predictive tool to help guide patient selection for immunotherapy."
The VIGex signature, based on the expression level of 12 key genes involved in adaptive immune responses, classifies tumor samples into hot, intermediate-cold (I-Cold), and cold subgroups. The VIGex-Hot subgroup has been associated with better immunotherapy outcomes.
Combined Analysis of VIGex and Liquid Biopsy
The study, an international collaboration including researchers at the Princess Margaret Cancer Centre, analyzed the performance of VIGex and other biomarkers in an independent dataset of patients treated with pembrolizumab in the INSPIRE phase II clinical trial. The VIGex-Hot subgroup was associated with higher overall survival and progression-free survival.
Alberto Hernando-Calvo, Medical Oncologist at Vall d’Hebron and Core Phase 1 Investigator of VHIO’s UITM-CaixaResearch, explained, "We investigated the combined performance of ctDNA changes and other biomarkers including tumor mutational burden, PD-L1 expression using immunohistochemistry, and levels of ctDNA by liquid biopsy. We have found that the use of VIGex categorization of tumor samples pre-treatment and analysis of changes in ctDNA dynamics detected by liquid biopsy improves prediction of response to immunotherapy."
Hernando-Calvo further noted, "If a patient’s tumor sample pre-treatment with immunotherapy was classified as VIGex-Hot and a decrease in the quantity of ctDNA in plasma was observed during the first two treatment cycles compared with baseline, this associated with greater clinical benefit."
Future Steps for Biomarker Validation
"While our findings provide proof-of-principle for the combined use of VIGex classification and ctDNA dynamics to improve immunotherapy response prediction, these results are retrospective. Future prospective studies are required to establish the clinical utility of this approach for patient selection and guiding tailored immunotherapy treatment decisions," said Alberto Hernando-Calvo.
A phase III clinical trial, sponsored by the European Organisation for Research and Treatment of Cancer (EORTC) and the Asociación Española Contra el Cáncer - AECC, will assess the efficacy of immunotherapy plus radiotherapy in patients with squamous cell carcinoma of the head and neck. This study will evaluate the use of VIGex and ctDNA dynamics by liquid biopsy to prospectively establish the clinical utility of this predictive biomarker combination.
