Improving rare and untreatable cancer treatment in 2023 - the role of genetic testing

The availability of comprehensive multigene sequencing panels has generated enormous opportunities for linking novel therapies based on genomic findings in rare and refractory cancers. While molecular targeted therapies have achieved overwhelming success in selected cancer types, applying a broad strategy to tailor drugs against oncogenic alterations has not attained the same level of benefit. Recently, we have shown that evidence based drug selection remains crucial to demonstrate a survival benefit in the molecular screening and therapeutics (MoST) cohort.1 While significant survival differences have been observed in patients who received matching therapies in Therapy-Oriented Precision Oncology Guidelines for Recommending Anticancer Pharmaceuticals (TOPOGRAPH) Tiers 1–3, no advantage over unmatched therapies was seen in patients who received therapies still in early development (Tiers 3B/4).2,3 Specifically, drug repurposing based solely on genomic biomarkers yielded no observable survival difference, reinforcing that clinical trial participation remains highly relevant rather than off-label use. Accessing biomarker-linked trials remains challenging in Australia; integrating informatic tools to locate relevant trials and improve referral pathways may reduce the disparity in oncologic care from genomic biomarker testing. Multidisciplinary collaborations between oncologists, pathologists, regulators, and stakeholders in drug development must take place to usher in the promise of precision oncology in the coming decade. References 1. Thavaneswaran S, et al. Cancer Molecular Screening and Therapeutics (MoST): a framework for multiple, parallel signal-seeking studies of targeted therapies for rare and neglected cancers. Med J Aust 2018; 209: 354–355. 2. Lin F, et al. Criteria-based curation of a therapy-focused compendium to support treatment recommendations in precision oncology. NPJ Precis Oncol 2021; 23; 5: 58. 3. Lin F, et al. J Clin Oncol 2022; 40 (16_suppl): 3073.