Ghassan K. Abou-Alfa, MD:The patient here progressed within 11 months after sorafenib, which is not really a surprising event, but at the same time, it’s not a discouraging event. Usually, the median time on sorafenib is about 5 months or so, so 11 months is totally appropriate and reasonable. The good news is that this patient really had a very good tolerance of the sorafenibdid not require dose adjustments with the grade 1 hand-foot syndrome and grade 1 hypertension. And, as such, based on the recent data and the approval of regorafenib, the patient is eligible for regorafenib as a standard of care, second-line after failing sorafenib.
Regorafenib is quite an intriguing drug because it really came out of the blue with very positive results after progression of sorafenib. To debrief everybody, patients who were on sorafenib really progressed. They did not tolerate sorafenibthey really progressed on sorafenib—and were offered regorafenib versus placebo. Patients on regorafenib had a median survival time close to about 10.5 months in second-line compared to the placebo, which was close to about 7.5 months. So, clearly, there is an evident progression of disease followed by a control of the cancer one more time, with an improvement in survival.
There are several very important effects here. Number 1 is thatsurprisingly, but at the same time, nicely—patients were able to have a response rate on the regorafenib after sorafenib. We know it’s a real story. Number 2 is that some people wonder if maybe patients did not receive enough sorafenib, maybe a little bit of sorafenib, followed by regorafenib. Interestingly, in the study, which is now published inTheLancetjournal, it appears that the median time on sorafenib was about 7 months. So, it’s a real experience with sorafenib, same like our patient here today.
After this, the time between the sorafenib and the regorafenib was actually allowed to be a certain period of time in the clinical trial, and people were wondering if the trial super-selected patients who were having rather a good prognostic outcome. Surprisingly, they were only off the sorafenib and starting the regorafenib within a median of 28 days. So, clearly, this is a real story about people who received sorafenib, progressed on it, and then ultimately received regorafenib.
An important factwhich actually was mentioned in one of the presentations by Dr. Bruix, who was the first author of the regorafenib study, at the ILCA meeting in Vancouver in September 2016—is, in an unplanned analysis, the additional or additive effect of the sorafenib followed by regorafenib will lead to a cumulative median survival of 26 months. That was unheard of before. Remember, back before 2007, we were talking about 6 months’ median survival. We moved to about 10 months with sorafenib, and now we’re talking about 2 years-plus in regard to median survival. So, this is a clearly important story, and by all means, I can see the patient here—with the approval of the drug now and his tolerance of the sorafenib beforehand—should be on regorafenib.
Transcript edited for clarity.