No trend toward overall survival benefit in either trial arm. The PRECEDENT trial was not statistically powered to show a survival advantage and the results of the trial did not indicate a trend toward benefit in either arm (hazard ratio of 1.099 in the intent-to-treat population). While the median overall survival in the EC145 study arm of 14.1 months represented an improvement in relation to historical trials of PLD alone, the PRECEDENT trial PLD control arm had an unprecedented median overall survival of 16.9 months. These results may have been influenced by prognostic factors favoring the PLD control arm. Specifically, the level of sensitivity to post-trial platinum therapy as measured by platinum-free intervals may have been a factor. Patients in the PLD control arm received post trial platinum-based therapy at nearly twice the rate of those in the EC145 study arm, 33% versus 18% respectively. On an adjusted basis, which accounts for potential differences in demographics and prognostic factors such as platinum free intervals, the overall survival hazard ratio in the FR(++) group was 0.495, although the result was not statistically significant. --------
tough sell with the control arm doing better than the test arm, no?
Sure, OS data wasn't good. But, PFS data is very strong and this is apparently a high unmet medical need. ECYT also disclosed in the CC after this data was announced that apparently two Phase 3 trials demonstrating PFS benefit would be sufficient for U.S. approval (#msg-70634907). If this is indeed true, it sounds like they could gain approval even if they don't show an OS benefit in Phase 3, presumably because this is an indication with a high unmet medical need. It's not clear to me right now if they will run the two Phase 3 trials, though, and hopefully we get more guidance on this from the CC next Tuesday. It will also be interesting to see if they are filing for the accelerated approval in Europe, based on input from regulators there. And on the OS endpoint, I like that they at least put forth a rationale as to why this data may have been disappointing (issues with control arm receiving nearly twice the amount of platinum-based therapy post trial). Who knows if accounting and adjusting for this will result in them being able to show OS benefit in Phase 3, but at least they have a rationale.
I was initially as skeptical as you but I have since done a 180 on ECYT and actually have a position now.
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