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RESEARCH PRODUCT

In the literature: October 2020.

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Immune checkpoint inhibitors are widely used as treatment for an increasing number of solid tumours. Nevertheless, the lack of predictive biomarker represents a limitation across several cancer types. During the last years, the possibility to dynamically study tumour evolution through circulating tumour DNA (ctDNA) in plasma has opened novel possibility in evaluating disease status and therapeutic response, especially in localised disease to predict the possibility of relapse. However, the specific opportunities for application in the context of immunotherapy remain to be clarified.1 In an article recently published in Cancer Discovery by Zhang et al ,2 a comprehensive analysis of ctDNA data from about 1000 patients with 16 different solid tumour types, being the most represented non-small-cell lung cancer (NSCLC), urothelial, microsatellite instability high, gastro-oesophageal and ovarian cancers, treated in three phase I/II trials of durvalumab alone or in combination with tremelimumab, was presented. The aim was to characterise the prognostic and predictive value of pre and on-treatment ctDNA analysis, using training and validation sets. It was shown that ctDNA is detectable in most patients with important disease-specific differences. Pretreatment ctDNA level appears to be an independent, inversely prognostic variable across tumour types, characterised by an association with overall survival and other known prognostic variables, but not with overall response rate. On the other hand, on treatment ctDNA dynamics appear to be predictive of long-term benefit from immunotherapy across tumour types. The last point is of clinical interest as ctDNA fills an important unmet need as a complement to radiological assessments of benefit. Radiological stable disease is a common and particularly challenging clinical category, composed of patients with slowly progressive disease, indolent non-responding disease and radiologically subtle responses to immunotherapy.3 It was demonstrated that molecular response, defined by ctDNA dynamics, can help differentiatepatient who will ultimately derive benefit …