NGS testing is now recommended also for patients with some rare tumours and to detect tumour-agnostic alterations
As the body of knowledge about the molecular landscape of cancer continues to grow, the ESMO Precision Medicine Working Group (PMWG) has updated the Society’s recommendations for the use of tumour next-generation sequencing (NGS) to encompass patients with advanced breast cancer and some rare tumours, and to detect tumour-agnostic alterations in patients with metastatic cancers where access to matched therapies is available.
In 2020, a first version of the ESMO recommendations was released to inform clinicians about whether and how tumour multigene NGS could be used to profile frequent metastatic cancers (Ann Oncol. 2020 Nov;31(11):1491-1505). Research methodology consisted of identifying all recurrent genomic alterations in the eight cancers that were associated with the highest number of deaths in the world, and then ranking them according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). The first work of the expert group lead to support the use of NGS in advanced non-squamous NSCLC, prostate, ovarian cancers and cholangiocarcinoma.
The updated manuscript of the PMWG, published today in Annals of Oncology (Ann Oncol. 2024; Articles in press), confirms the previous set of recommendations and further expands them to reflect the recent advances in the field of precision oncology. For advanced breast cancer, for example, the ESMO recommendations are to perform testing of a tumour or plasma sample from a patient with hormone receptor-positive/HER2-negative tumour as standard of care following the reclassification of ESR1 mutations to level IA of the ESCAT scale based on the demonstrated antitumour efficacy of elacestrant in this population (J Clin Oncol. 2022 Oct 1;40(28):3246-3256), and considering that tumour NGS can substitute germline BRCA1/2 testing in most of the patients. Also, the NGS testing should be done after resistance to endocrine therapy to optimise the likelihood of detecting ESR1 mutations.
Based on the number of alterations currently classified as level I of the ESCAT scale in rare tumours, the ESMO recommendations are to perform tumour NGS in patients with gastrointestinal stromal tumours (GIST), sarcoma, thyroid cancer, and cancer of unknown primary (CUP). Finally, NGS testing is recommended to detect tumour-agnostic biomarkers such as NTRK1,2,3 fusions, RET and FGFR1/2/3 fusions/mutations, BRFAV600E mutations, MSI-H, and TMB-H, which are classified as level I based on the clinical improvement of patient outcomes in recent basket trials. Given that the approval of therapies to target specific oncogenic variants regardless of tumour histology is currently limited to some geographical areas, testing is recommended only in countries where treatments are accessible, encouraging a careful assessment of its cost-effectiveness at a local level.
The update of the ESMO recommendations for the use of NGS is part of the Society’s ongoing efforts to build a framework for precision medicine that reaches all patients who can benefit from it. Currently, access to more advanced technologies including NGS panels is still highly heterogeneous both across Europe and within individual countries, mainly due to costs of technologies and reimbursement policies, as an ESMO study revealed in 2023.
