Table 1.

ESMO Scale for Clinical Actionability of molecular Targets (ESCAT).

ESCAT evidence tier	Level of evidence A	Level of evidence B	Level of evidence C	Clinical implications
I: Alteration-drug match is associated with improved outcome in clinical trials	Prospective, randomized clinical trials show the alteration drug match in a specific tumor type results in a clinically meaningful improvement of a survival end point	Prospective, non-randomized clinical trials show that the alteration-drug match in a specific tumor type, results in clinically meaningful benefit as defined by ESMO MCBS 1.1	Clinical trials across tumor types or basket clinical trials show clinical benefit associated with the alteration- drug match, with similar benefit observedacross tumor types	Access to the treatment should be considered standard of care
II: Alteration-drug match is associated with antitumor activity, but magnitude of benefit is unknown	Retrospective studies show patients with the specific alteration in a specific tumor type experience clinically meaningful benefit with matched drug compared with alteration- negative patients	Prospective clinical trial(s) show the alteration- drug match in a specific tumor type results in increased responsiveness when treated with a matched drug, however, no data currently available on survival end points	NA	Treatment to be considered ‘preferable’ in the context of evidence collection either as a prospective registry or as a prospective clinical trial
III: Alteration-drug match suspected to improve outcome based on clinical trial data in other tumor type(s) or with similar molecular alteration	Clinical benefit demonstrated in patients with the specific alteration (as tiers I and II above) but in a different tumor type.Limited/absence of clinical evidence available for the patient- specific cancer type or broadly across cancer type	An alteration that has a similar predicted functional impact as an already studied tier I abnormality in the same gene or pathway, but does not have associated supportive clinical data	NA	Clinical trials to be discussed with patients
IV: Preclinical evidence of actionability	Evidence that the alteration or a functionally similar alteration influences drug sensitivity in preclinic in vitro or in vivo models	Actionability predicted in silico	NA	Treatment should ‘only be considered’ in the context of early clinical trials. Lack of clinical data should be stressed to patients
V: Alteration-drug match is associated with objective response, but without clinicallymeaningful benefit	Prospective studies show that targeted therapy is associated with objective responses, but this does not lead to improved outcome			Treatment should ‘only be considered’ in the context of early clinical trials. Lack of clinical data should be stressed to patients. Clinical trials assessing drug combinationstrategies could be considered.
X: Lack of evidence for actionability	No evidence that the genomic alteration is therapeutically actionable			The finding should not be taken into account for clinical decision