The significance of tissue-agnostic biomarkers in solid tumors: the more the merrier?

ABSTRACTIntroduction To date, several emerging biomarkers have gained considerable interest in the field of predictive molecular oncology. The advent of precision medicine has led to the development of innovative drugs targeting rare molecular pathways independently from histology, defined as tissue-agnostic drugs.Areas covered Although there is a lot of promise for this new tissue-agnostic model in the oncological scenario, crucial issues from both the diagnostic and therapeutic standpoint are emerging. This review aims to critically examine the role of tissue-agnostic biomarkers in different solid tumors, focusing on the prevalence and methods of detection of agnostic biomarkers together with drug approvals to guide clinicians in this evolving landscape.Expert opinion To strengthen the framework for tissue-agnostic approvals, the dialogue between regulatory, industrial, and academic parties should be intensified. Critical questions include the development of an efficient network system that can overcome the heterogeneity of patients’ inclusion criteria along with the increasingly difficult interpretation of next-generation sequencing (NGS) profiling technologies. Cost-effectiveness and risk–benefit studies are needed in the national context considering the modalities of access to diagnostic tests and reimbursement of treatments.KEYWORDS: NGSpredictivebiomarkerstissue-agnosticMTB Article highlights The wide adoption of next-generation sequencing (NGS) technologies has resulted in shifting precision medicine toward a pan-cancer approach, using tissue-agnostic biomarkers for the selection of appropriate treatments according to specific molecular targets.The advent of precision medicine has led to the development of innovative drugs targeting rare molecular pathways independently from histology, defined as tissue-agnostic treatments.To date, genomic alterations within NTRK, BRAF, RET genes together with the evaluation of MSI/dMMR and TMB status certainly represent the novel and most promising histology-agnostic biomarkers where the keywords for the real-world implementation, however, remain applicability, homogeneity, and economic feasibility of the required genomic tests.Tissue-agnostic drugs are usually tested in basket trials often featuring heterogeneous study population and results, leading to considerable difficulties in evaluating the real efficacy of the drug and consequently the reimbursement approval by regulatory agencies.Cost-effectiveness and risk–benefit studies are needed in the national context considering the modalities of access to diagnostic tests and reimbursement of treatments.AcknowledgmentsM.LM. and M.P. contributed to this work under the Doctoral Program in Experimental Oncology and Surgery, University of Palermo.Declaration of interestValerio Gristina has received honorarium for advisory boards from Bristol Myers Squibb and IQVIA, speaker honorarium from Novartis, MSD, Astrazeneca for work performed outside of the current study. Pasquale Pisapia has received personal fees as speaker bureau from Novartis for work performed outside of the current study. Giancarlo Troncone has received personal fees (as speaker bureau or advisor) from Roche, MSD, Pfizer, Boehringer Ingelheim, Eli Lilly, BMS, GSK, Menarini, AstraZeneca, Amgen, and Bayer for work performed outside of the current study. Antonio Russo has received honorarium for advisory boards from Bristol Myers Squibb, Pfizer, Bayer, Kyowa Kirin, Ambrosetti, and speaker honorarium from Roche Diagnostic and Astrazeneca for work performed outside of the current study. Umberto Malapelle has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientific, Eli Lilly, Diaceutics, GSK, Merck and AstraZeneca, Janssen, Diatech, Novartis and Hedera for work performed outside of the current study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewers disclosurePeer reviewers in this manuscript have no relevant financial relationships or otherwise to disclose.Additional informationFundingThis paper was not funded.