Table 7.

Agnostic therapy: take home messages

Molecular Markers	Take home messages
TMB	● The determination of TMB on peripheral blood is not yet standardised in the absence of a well-defined cut-off ● Further studies are needed to confirm the reliability of liquid biopsy in determining TMB compared to tissue analysis
MSI	● Actually two NGS-based approches are FDA-approved blood-based diagnostic tests and are considered suitable for the determination of MSI on peripheral blood samples
NTRK fusion	● Currently the potential of liquid biopsy in identifying NTRK fusions should be further explored ● In some reports, plasma-based NGS tests have shown a high degree of concordance with tissue genomic tests for several genetic mutations, including NTRK fusions
BRAF	● Most of the published literature on the clinical use of liquid biopsy to detect patients with BRAF mutation concerns maily mCRC, melanoma and NSCLC, while few data are available on less frequent types of cancer ● Liquid biopsy in the determination of Braf mutations should be further explored in patients with different types of solid tumours
PI3K mutation	● Further studies are needed to assess whether alpelisib may have an agnostic indication in solid tumours carrying the PI3KCA mutations ● Liquid biopsy has been extensively studied and currently approved to detect PI3CA-mutated breast tumours

Further trials to validate and standardise analysis techniques in solid tumours are urgently needed to expand the use of liquid biopsy in clinical practice for the agnostic indications