Advanced cancers, more chance of cure with extended genomic profiling

More than 30% of patients with advanced cancer today can receive therapy based on a biomarker, i.e. a genetic-molecular alteration. This percentage is destined to increase, thanks to advances in research and the new paradigm of precision oncology, consisting of the mutational model, in which the genomic signature exceeds the value of the organ from which the cancer originates.

For this new approach to work effectively, on the one hand, it is necessary to use extensive genomic profiling tests, with panels that can examine as many as 500 genes with a single test, such as Ngs (Next Generation Sequencing) tests. On the other hand, discussion by Molecular Tumour Boards (Mtb) is indispensable to assess the biological and clinical significance of the alterations detected, which could be treated with specific molecular-targeted drugs or immunotherapy.

But in Italy only 2% of biopsies from cancer patients are analysed with Ngs (in 2020/2021), against a European average of 10%. And to date, only 12 out of 21 local health systems have a single regional Ngs. For the mutation model to become established, it is essential that a structured Mtb network is set up, in close collaboration with the regional oncology networks, and a national Molecular Tumour Board coordination centre, which monitors the establishment and activities carried out at regional level. The request comes from the 'Italian Summit On Precision Medicine', an international event organised by the Foundation for Personalised Medicine (Fmp), held in Rome with over 150 experts.

The mutational model is a challenge for oncology, enabling new treatment strategies, combined with truly innovative scientific and regulatory pathways, with the need to ensure equal access for all patients. In the histological model, drugs are authorised by the European regulatory body, reimbursed by national regulatory agencies and prescribed by oncologists. The mutational model is distinguished by its focus on patients with metastatic disease, for whom conventional treatment options do not provide satisfactory results. These patients could benefit from targeted treatments based on the recognition of specific mutations, which, however, in almost all cases, lack documented scientific evidence, with the consequent problem of access to these therapies, which are not yet authorised or reimbursed by the National Health Service. In the mutational model, drugs are indicated by the Molecular Tumor Board following genomic profiling of metastatic patients for whom standard treatments have failed to show benefit. In this new paradigm, treatments are off-label in the presence of mutations with a different site than the authorised one or because they are drugs in the development phase and therefore not yet authorised and reimbursed. The most complex aspect concerns the access and financial coverage of therapies according to the decisions taken by the Mtb.

In 2024, 390,100 new cancer diagnoses are estimated in our country. In Italy, we need to speed up the establishment of Molecular Tumor Boards, because they are the only bodies capable of exploiting the potential of mutational oncology. The analysis and interpretation of the results of genomic profiling require inter- and multidisciplinary skills. It is therefore essential to set up Molecular Tumor Boards, in which professionals from different areas are involved, such as, for example, the medical oncologist, the anatomopathologist, the molecular biologist, the geneticist, the clinical pharmacologist, the hospital pharmacist, the bioinformatician, the clinical epidemiologist and the bioethicist. Multiple competences are integrated in these realities, to govern the clinical and decision-making processes of appropriateness. At present, in Italy, MTBs have only been set up in a few regions, with a significant lack of homogeneity in the definition of patients to be subjected to genomic profiling, in the identification of the characteristics of the Ngs test to be used and in the methods of economic coverage of the pharmacological treatment proposed by an MTB. In addition, a crucial objective is the sharing of uniform genomic data through the completion of the National Genomic Platform, which will enable the production of new knowledge and the access of more patients to innovative therapies, while at the same time enabling the evaluation of effectiveness and costs and better governance of clinical practice.