Currently, the choice of biologics in the personalised setting are anti-EGFR or anti-VEGF therapy.

Previous studies suggested inconsistent results so in the clinical practice setting we don’t draw any

conclusions about what are optimal biologics in the first line setting. So looking at the US

circumstances, bevacizumab is more used in the first line setting over anti-EGFR therapy but a

previous study suggested anti-EGFR is more sensitive in the RAS wild-type left sided tumours. Based

on that data we started a paradigm study with RAS wild-type left sided tumours in the first line setting.

The paradigm study is a first, prospective study to test the superiority of panitumumab over

bevacizumab in combination with a modified FOLFOX6 treatment for the personalised setting for this

patient population. The primary endpoint is overall survival in the left sided population, defined as

descending colon, sigmoid colon, rectosigmoid or rectal.

The findings in this study for the primary endpoint show panitumumab has demonstrated superiority in

the overall survival over bevacizumab with a hazard ratio of around 0.80. So I believe that this has

statistical significance. This trial showed the primary endpoint was met.

This study also was conducted in a hierarchical way and the second primary endpoint, overall survival

in the overall population, defined as left and right sided primary tumour both. We conducted a

statistical analysis showing superiority of overall survival in panitumumab over bevacizumab in the

overall population as well.

So these are the two key findings and there are also additional key findings shown here that the R0

curative resection rate by treatment panitumumab is better than bevacizumab, the average score is

80% versus 10% respectively. So I believe that the panitumumab patients who were allocated

panitumumab plus modified FOLFOX6 have the chance of a cure, [INAUDIBLE] compared to the

bevacizumab allocated patients.

Adverse events, first of all I want to say that no unexpected signal was observed in this study in both

arms. However, acne-like dermatitis, stomatitis, paronychia, hypomagnesaemia, [INAUDIBLE] were higher

with panitumumab than bevacizumab. But I believe that [INAUDIBLE] balancing between efficacy and

safety, I still believe that efficacy over safety. So I believe that [INAUDIBLE] panitumumab FOLFOX is the

most promising treatment so far from now.

The take-away message from me is that this study suggested panitumumab plus modified FOLFOX6

is a new standard of care clinically over bevacizumab plus modified FOLFOX6 in patients with RAS

wild-type left sided primary tumours. It’s my message, that.