We published a randomised phase II trial of ramucirumab combined with docetaxel and compared that to docetaxel alone in those patients who had previously received chemotherapy for metastatic disease for urothelial carcinoma. In that trial we demonstrated a doubling of the progression free survival in favour of ramucirumab and docetaxel compared to docetaxel alone. Additionally the survival was trending in the right direction although we did not power the trial to look at a survival endpoint. We also saw about a doubling in the objective response rate in those patients treated with ram/doce compared to docetaxel alone.

So the RANGE trial was designed to confirm this in a phase III setting. Again it compared ramucirumab given 10mg/kg every three weeks along with docetaxel 75mg/kg to docetaxel 75mg/kg. These were a poor risk group of patients, 80% had at least one Belmont risk factor and about 13% of patients had haemoglobins of less than 10. So this is a group that you would expect to do poorly. About 10% of patients had prior checkpoint inhibition therapy. This trial was designed before the era of checkpoint therapy for metastatic urothelial carcinoma.

What we demonstrated was again a similar improvement in progression free survival. It’s a 25% reduction in the rate of progression in favour of ramucirumab and docetaxel compared to docetaxel alone. We had about a doubling of the objective response rate, approximately 24.5% of patients with ram/docetaxel demonstrated an objective response; about 14% with docetaxel alone. We did not see any significant cost in toxicity, in fact if we look at the EORTC quality of life scales they are exactly the same for patients who received ram/doce versus doce alone. So we concluded that this is a viable treatment option for those patients with previous chemotherapy for urothelial carcinoma. It’s the first trial to demonstrate a progression free survival benefit for those patients treated with anti-angiogenesis therapy and chemotherapy.