Although precision medicine holds the promise of bypassing the traditional ‘one size fits all’ approach in oncology – helping in the selection of treatments that best improve outcomes for each individual patient – its real-life use is not yet meeting up to its theoretical actionability. Will precision medicine deliver hope to cancer patients or is it just all hype? A panel of experts will try to address this legitimate question in a Patient Advocacy Session at ESMO Virtual Meeting 2020.
“Our ability to provide precision medicine to patients has greatly improved over the last couple of years and the pace of change is increasing – we have more targeted drugs and more amenable regulatory pathways,” highlights Dr Rodrigo Dienstmann, Oncoclínicas Precision Medicine, São Paulo, Brazil and Vall d'Hebron Institute of Oncology, Barcelona, Spain, one of the session’s speakers. “We have now also advanced our knowledge of tissue agnostic biomarkers, which may help clinicians select targeted treatments irrespective of the tumour type.”
Recently, ESMO released the first recommendations from a scientific society about the use of multi-gene next-generation sequencing (NGS). The recommendations were developed by the ESMO Translational Research and Precision Medicine Working Group on the basis of the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) ranking for genomic alterations occurring in the eight cancers responsible for the most deaths worldwide. ESMO’s recommendations represent a key step in guiding clinicians toward a more conscious evidence-based use of multi-gene NGS in clinical practice; however, some obstacles still slow down progress in the field.
“The delivery of precision medicine remains restricted by our capability to interpret the genomic alterations and match them with the most appropriate targeted agents or immunotherapies. Currently, access to the most promising anti-cancer medicines is not often guaranteed to all patients.” The cost of genomic analyses and affordability of treatments are two key limiting factors to a successful integration of precision medicine into daily routine. The use of NGS or comprehensive molecular analysis of tumours is still very expensive and, in some countries, is restricted to academic settings or insured patients. “Clinicians may know that assessing single gene alterations in a consecutive manner will provide an incomplete answer,” says Dienstmann, “but high costs prevent comprehensive analyses from being ordered. He adds that “multi-gene NGS tests have already passed the tipping point for broad utility in some tumour types, such as lung adenocarcinomas, based on efficiency in cost and tissue use.”
ESMO recommends that clinical research centres develop multi-gene NGS as a tool to screen patients eligible for clinical trials and to accelerate drug development, and prospectively capture the data that could further inform how to optimise the use of this technology. Dienstmann reinforces that “for most tumour types, at the individual patient level, we should calibrate the expectations given the rarity of actionable alterations that have proven clinical impact. Also, clinicians should avoid dubious genomics-guided therapies off-label based on scant evidence. Access to molecular tumour boards are important to keep high standards for interpretation of NGS results and harmonised decision-making.” Another current issue is that NGS may reveal the presence of more than one oncogenic driver; however, the combination of targeted drugs to treat those alterations may not have been studied and approved. “I consider it malpractice to combine therapies for which the toxicity profile and efficacy data have not been reported in the literature,” adds Dienstmann.
The timing of NGS also needs to be right according to Dienstmann: “We have to balance testing a lot of alterations at the beginning, with being aware that there may be further genetic changes over time. Multi-gene panels are often used too late, when patients have failed all standard lines of therapy and a precision medicine approach is unlikely to be beneficial – this may give the patient false hope.” With some genomic alterations detected by NGS, there is a lack of knowledge about whether the targeted treatment is sufficiently effective to improve survival compared with non-precision medicine alternatives. The ESMO-Magnitude of Clinical Benefit Scale may help with prioritisation in certain cases, but the clinical value of using targeted treatments is not always known.
“Precision medicine requires a paradigm change in the management of cancer care – much progress is being made, but we have to think carefully before using this technology in daily practice,” concludes Dienstmann.
Patient Advocacy 2 - Precision medicine: Hopes and hypes, 17:10:2020, h. 12:10 – 13:30, Channel 5