Is precision medicine coming of age?

Rapid advances in high-throughput genomic technology are driving the evolution of precision medicine and genomic sequencing could eventually become a routine part of clinical practice.

This article was extracted from the Congress Daily News

Precision medicine has the potential to improve health outcomes, reduce toxicity and increase cost efficiency. Importantly, it puts the patient at the centre and allows physicians to optimise disease management.

Precision medicine puts the patient at the centre of treatment

Oncology will be one of the areas in which the impact of precision medicine will be greatest: it could transform cancer care in the coming decades. The power of precision medicine in oncology was first signalled by HER21, with its initial identification as a prognostic biomarker in breast cancer and the subsequent development of a HER2-targeted monoclonal antibody for treatment. This was followed by the emergence of a series of small molecule tyrosine kinase inhibitors, including imatinib, which transformed the survival prospects of patients with chronic myeloid leukaemia1 and gefitinib and erlotinib, which improved survival for patients with non-small-cell lung cancer (NSCLC) and specific activating mutations of the epidermal growth factor receptor (EGFR). Today, genomic sequencing is identifying genes central to cancer biology; this is already being applied both in clinical trials and clinical practice, as illustrated by the identification of the EML4-ALK fusion gene in NSCLC and targeting with crizotinib, which is now available in many countries for the treatment of ALK-positive NSCLC.

While precision medicine has the potential to redefine every aspect of patient care, it does have limitations. Not all molecular alterations are predictive of response to a specific targeted treatment nor are they all druggable. Echoing this note of caution, Professor Charles Swanton from London Research Institute, UK, in a Special Session on Monday, Precision Medicine: Panacea or False Dawn, mentioned that genomics may not be quite so simple. Drivers of tumour growth may change during tumour evolution and treatment and the identification of sub-clonal driver events will limit the efficacy of single-agent targeted therapy. The need for repeat tumour samples to monitor these effects has opened up the field of liquid biopsies, said Professor Andrew Hughes from Macclesfield, UK. He also spoke of the emergence of new clinical trial designs, such as the so-called basket designs, to manage the investigations of targeted agents in smaller groups of patients.
Concluding the session, Dr Johann De Bono from the Royal Marsden Hospital NHS Foundation Trust, Sutton, UK, and Chair of the ESMO 2014 Scientific Steering Committee, said that, “The presentations highlight how challenging [delivering precision medicine] is, but there is significant promise.”

Other issues which may delay the wider adoption of precision medicine may include: the cost of molecular sequencing; validation of specific biomarkers; the availability of molecularly targeted drugs; access to clinical trials; and managing patient expectations. Healthcare professionals will need to adapt to increasing challenges in the analysis of molecular data and the complexities involved in both informing patients about several clinical trials and then allocating them to the most promising trial protocol. Ethical issues, such as revealing increased risk and false-positive/false-negative results, are also a concern.

Precision medicine is based on the precept that detailed molecular characterisation of the patient’s tumour and its microenvironment will enable tailored therapies to improve outcomes and decrease toxicity. However, there are numerous challenges we need to overcome before delivering on the promise of personalised cancer therapy. These include tumour heterogeneity and molecular evolution, the costs and potential morbidity of biopsies, lack of effective drugs against most genomic aberrations, technical limitations of molecular tests, and reimbursement and regulatory hurdles. Critically, successes and limitations surrounding personalised cancer therapy must be tempered with realistic expectations, which, today, encompass increased survival times for only a proportion of patients.

1. Ciardiello F, et al. Ann Oncol 2014;25:1673–8