BIOMARKERS
there have been an additional 21 drugs approved for an additional 10 genomic indications. Two terms are important to clarify in this context: ‘genome-targeted’ drugs are those approved for use based on genomic test results, and the drug targets the aberration detected by that test, while ‘genome-informed’ therapies are those drugs that are given after a genomic test, including all genome-targeted drugs, regardless of whether the drug was meant to target the abnormalities found in the test or acted via an alternative mechanism of action (
https://www.sciencedirect.com/science/article/ pii/S0923753421011212?via%3Dihub). Analyses show that for genome-targeted
therapy, estimated eligibility was 5.1% in 2006, which then rose to 8.8% by the end of 2018, and has since increased to 13.6% in 2020. For genome-informed therapy, estimated eligibility was 10.7% in 2006, 16.5% in 2018, and 27.3% in 2020. For genome-targeted therapy, median duration of response was 18.9 months (range, 5.7 months to 80 months) in 2006 and 17.6 months (range, 4.6 months to 80 months) in 2020 and the median response rate was 19.0% (range, 10.6% to 95.3%) in 2006 and 63.5% (range, 12.0% to 95.3%) in 2020. For genome-informed therapy, estimated response was 3.3% in 2006, 7.7% in 2018, and 11.1% in 2020. Therefore, with an increasing number of people who are both eligible for, and respond to, genomic therapies, it is essential to consider access to genomic testing, the importance of testing both DNA and RNA, and consider tissue and liquid biopsy testing, given that liquid biopsies may help identify additional alterations. We are getting better at addressing some of the questions through clinical trials, and accumulating prospective testing in routine practice in this context are: a) optimising timing of tissue and blood testing; b) gaining experience and realising the benefit of using fresh versus archival tissue specimens; c) conducting tests on broad-based platforms versus spot testing; d) using in-house or outsourced testing solutions; e) weighing out the need for rapid turnaround time to results; and f) reimbursement strategies.
In the current landscape of oncology practice, >40% of biomarker mentions are still in the context of predicting response to therapy. Phase 3 trials have disproportionately more biomarkers for inclusion criteria and predicting therapy response (~54%), and few trials for response monitoring (~6%), which is particularly notable in the era of the
“Oncology indications will continue to multiply in parallel with drug development. These call for the rapid incorporation of biomarkers into development and validation efforts”
rapid growth of immunotherapies (IO), such as checkpoint inhibitors. In the field of IO, biomarkers available today could be classified into three categories: a) biomarkers that tell us if the tumour is ‘inflamed’; b) those that reveal the ‘immunogenicity’ of the tumour – that is, how likely is it to engage an immune response; and c) the biomarkers of the ‘host’ factors (
https://www.frontiersin.org/ articles/10.3389/fcell.2020.00155/full). Access to biomarker testing varies across sites and geographies. Community practices generally only have access to IHC (immunohistochemistry), and, to a lesser extent ELISA (enzyme-linked immunosorbent assay), flow cytometry and, PCR/ NGS platforms. Therefore, some of the main drivers for centralisation of biomarker testing are lack of in-house expertise (eg, bioinformatics, interpretation, scoring) and lack of test request volume. While drivers for de-centralisation may represent reduced turnaround with local testing, preference for internal processes, keeping control of samples and favourable costs in the long run. Armed with an ever-growing armamentarium of candidates and some validated biomarkers, as well as with an increasing understanding of the complexities dictating response to anti-cancer therapies, we can now state that one-biomarker- integration of the local, tumour and peripheral biomarker monitoring, utilising multiple techniques and methods, is necessary at multiple time points throughout anti-cancer treatment, to obtain a systemic, organ, tissue, cellular and molecular personalised, patient-orientated approach. Oncology indications will undoubtedly continue to multiply, in parallel with unprecedented drug development efforts to bring novel therapies to life. These collective endeavours call for the rapid incorporation of biomarkers into development and validation efforts, as an integral and indispensable component for ultimate routine practice and
| 31
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50
