Do more targets allow more cancer treatments, or not?

The three current oncology models (histological, agnostic and mutational) mainly differ in clinical, technological and organisational aspects, leading to different regulatory procedures and implications in antineoplastic therapy access by patients. Within the histo-logical and agnostic models, Regulatory Agencies authorise target therapies and define their price, reimbursement, prescription and access based on results from clinical trials including patients affected by the same tumour (histological) or subjects with specific genetic mutations regardless of the tumour site or the histology (agnostic). The mutational model has been developed to identify specific actionable molecular alterations found by next-generation se-quencing test-based large platforms on solid and liquid biopsies. Nevertheless, due to the highly uncertain efficacy and possible toxicity of drugs tested within this model, regulatory procedures based on histological or agnostic oncology cannot be followed. Multidisciplinary skills are required (e.g. the molecular tumour board's (MTB) representatives) to identify the best association between the genomic profile and the drug planned to be used, but quality requirements, practices and procedures of these discussions still need to be standardised. Real -world evidence from clinical practice (i.e. genomic findings, clinical data and MTBs' choices) lacks, therefore, it is urgently needed as opposed to limited findings from clinical trials. A potential solution for an appropriate access to the therapy chosen by the mutational model can be the indication-value-based sub iudice procedure of authorisation. The access to therapies suggested by extensive molecular profiling could be easily implementable within the Italian national health system, thanks to the existing regulatory procedures, i.e. the managed- entry agreements and the antineoplastic drug monitoring registries, alongside those granted by conventional studies (phase I, II, III, IV) conducted according to the histological and agnostic models.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

The three current oncology models (histological, agnostic and mutational) have different regulatory procedures and implications in antineoplastic therapy access. Regulatory Agencies in histo-logical and agnostic models authorize target therapies and define their price, reimbursement, prescription and access based on clinical trials. The mutational model requires multidisciplinary skills but lacks standardized quality requirements for discussions. Real-world evidence from clinical practice is urgently needed. An indication-value-based sub iudice procedure of authorization could be a potential solution for access to therapy chosen by the mutational model.