"MET activation is seen in a variety of different studies in HCC and we think having the combined activity is really important here. This is a trial with primary end point for overall survival and here we had data here at ASCO last year which seems like highly effective we got a pretty decent in a Phase II trial, non-randomized single arm we saw about 15 month OS" "15 month OS;"seems outstanding to me.It seems everyone has over looked that fact.I wonder what the experts think?
" "15 month OS;"seems outstanding to me.It seems everyone has over looked that fact."
Actually Clem, I have discussed the HCC results, including the 15.1 month survival statistic more than once. Let's look at the positive here and then just for Enabler's benefit, I will throw in some negative as well. 15.1 months was achieved in a 41 patient sample size, half of whom were Nexavar (sorafenib) refractory. 41 is a good size and that 15.1 statistic compares very favorably with the Nexavar result in its phase 3 in HCC which achieved a 10.7 month OS. The placebo arm of the Nexavar trial had a 7.9 month OS. What bothers me about this comparison is that the PFS for the Cabo trial was 4.4 months. Patients discontinue treatment at progression. I have to question that 15.1 month statistic in light of the fact that half the patients discontinued treatment at 4.4 months or less.
The Nexavar trial also measured time to progression, similar to PFS, except with TTP, patients who die prior to progression are censored, whereas with PFS it is counted as an event. This difference will artificially inflate TTP as compared to PFS. Because half of the Cabo patients had prior Nexavar, the presumption is that the Cabo patients were more heavily treated than the Nexavar patients. This may be misleading. 80% of the Nexavar patients had prior IFN or IL2. For comparison, 80% of Cabo patients had 1 or 2 lines of systemic therapy, 56% had prior TKI's. Perhaps more telling is that both trials required Child-Pugh A ratings. Sorafenib patients had a TTP of 5.5 months compared to Cabo's PFS of 4.4 months. For reasons mentioned earlier, those stats are artificially skewed in favor of Sorafenib, so I would call it a tie.
Stinkin Yahoo deleted one. All that said about the Cabo vs Sorafenib comparisons, the more relevant comparison is not S, but placebo. The Cabo HCC pivotal trial is Cabo vs placebo in S refractory patients. In the S trial, the placebo arm had a TTP of 2.8 months and OS of 7.9 months. S had a 3 month TTP advantage of placebo and that advantage carried over to the OS analysis (10.7 vs 7.9). I would expect a similar or better outcome for Cabo vs placebo.
From NEJMoa0708857, a Sorafenib trial vs placebo (caveat emptor regarding dosing duration and iteralia-ness): "Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group."