ESMO Theme: Personalized (“Precision”) Oncology Care Marches Forward

Caroline Helwick

October 2012, Vol 3, No 7 - Personalized Medicine

Vienna, Austria—“One of our themes at the 2012 ESMO Congress is personalized oncology,” European Society for Medical Oncology (ESMO) Presi­dent Martine J. Piccart-Gebhart, MD, PhD, Professor of Oncology at the Université Libre de Bruxelles and Director of the Medicine Department at Jules Bordet Institute, Brussels, Belgium, said at a press briefing at the meeting. She noted that the numerous presentations on targeted therapy and diagnostics at ESMO are evidence that the field is rapidly moving forward.

Elucidating the complex molecular architecture of cancer offers the promise of “precision medicine,” Dr Piccart-Gebhart said, because targeted molecular therapies are becoming standard in the treatment of most tumor types. But with this comes a massive amount of data derived from full genome sequencing, exome sequencing, DNA sequencing, RNA sequencing, and protein analysis.

The data from these analyses, as Dr Piccart-Gebhart pointed out, must be shared “efficiently” between academia, government, and industry. She predicted that it will take a “revolution” for this to occur sooner rather than later.

“We still have a long way to go before massive amounts of genetic alterations can be linked to cancer biology and translated into truly effective treatment strategies,” Dr Piccart-Gebhart noted.

But Do Molecular Markers Help in the Clinical Setting?
Several biomarkers are well established in the clinical setting, such as estrogen receptor status, HER2 status, epidermal growth factor receptor
status, and KRAS gene expression. In the past year, BRAF and ALK abnormalities have joined the list.

But Matthias Preusser, MD, Neuro-oncologist, Department of Internal Medicine, of the Medical University of Vienna, acknowledged, “For most cancers, molecular profiling is still not clinically validated, although there are plenty of encouraging data emerging, including from presentations here at ESMO, to suggest that this could change in the near future.”

He asked, “Can we look forward to a day when tumors are fully profiled for all known biomarkers as standard practice? And if they are, will clinicians know the full extent and implications of the results they receive and the nuances that particular combinations of markers signify in terms of treatment? Or will we continue to stick rigidly to standard therapies, perhaps afraid of the risks and repercussions of following nonstandard treatments?”

He noted that even as the pool of biomarkers expands, treatment decisions for many tumor types are still based on clinical factors, such as age and performance status, sometimes even when biomarkers have been clinically validated.

Addressing the use of molecular markers in patients with colorectal cancer, Alberto Sobrero, MD, PhD, Head of the Medical Oncology Unit at Ospedale San Martino in Genoa, Italy, maintained that oncologists are a long way off from using molecular markers to routinely guide treatment.

He said that although the determination of KRAS status was “paradigm changing,” it applies to the metastatic setting only. The initial management of patients with colorectal cancer is not driven by molecular markers. “We choose anti-VEGF [vascular endothelial growth factor] therapy (ie, bevacizumab) based on ‘nothing,’ and other molecular markers are weak,” Dr Sobrero pointed out.

Laboratory Assays for Markers Need Validation
“In my opinion, one major obstacle to bringing new biomarkers into use in everyday clinical work and for the benefit of patients is the lack of studies validating our laboratory assays,” Dr Preusser added. He called for more high-quality studies on the analytical performance of test methods—such as phase 1, 2, and 3 clinical trials for novel drugs—to determine which assays are best for a given biomarker.

“The use of biomarkers has provided a plethora of information in terms of tumor biology and sensitivity and resistance to treatment. However, not all types of cancer have biomarkers available for use. Actually, very few biomarkers are currently being used to guide treatment decisions,” agreed Evandro de Azambuja, MD, PhD, Medical Director of the Breast Data Centre and a member of the Ethical Committee at Jules Bordet Institute.

But the use of gene expression profiling has helped researchers, and now clinicians, understand tumor biology in several malignancies, with breast cancer at the forefront of this new approach. “So, without any doubt, we are progressing towards personalized medicine,” Dr de Azambuja said.

Dr de Azambuja also stressed the need to move from the current clinical trial model to one based on testing novel drugs in rationally selected patient populations, which was a theme echoed by many other investigators in presentations during the meeting.

“Clinical trials should no longer be conducted in unselected patient populations,” Dr de Azambuja suggested.