"Considering that checkpoint inhibitors are still undergoing pivotal clinical evaluation in NSCLC, it is absurd to suggest that Cabo has to paired with one. "
You may be a little out of touch with reality my friend. Also remeber ECOG study is in wtEGFR pts. Nivo will likly be approved for second line Adeno as quickly as they were approved in squamous. That was weeks not months as many will remeber.
I agree Ernie, there was nothing reported that couldn't have been easily inferred from the abstracts, I assumed the OS for the doublet in the ECOG would come in at about 13 months just based on the HR of 0.50 alone. I was in the audience this morning and don't belive we can move this forward as a doublet with erlotinib, especially given Nivos data presented yesterday morning, Cabo has to be paired with a check point and my concern would be the potential for a checkpoint inhibition to augment the toxicity associated with Cabo. We will have to see but it's not going to be an overly tolerable combo in my opinion. Still the data was strong and we'll see a nice bounce but this imo is no homer run,
Yes this is exactly what I was thinking. They need to look to combine with a Nivo in this setting. Single agent activity is not that higher than docetaxel but there is clear activity in the wtEGFR pt.
Just a point of clarification here, BMY did not drop today because of lack of efficacy in pts expressing less than 1% PDL1 on their tumors the stock dropped becusse the OS difference in 2nd line compared to docetaxel was less than expected. One thing I noted is docetaxel came in at over 9months. This is a bit higher than expected as about 8 months is more typical in this setting.
The big question now is if Cabo can do better than Nivo in this setting. We will know this answer to this very important question on Sunday. Of course with all the cautions associated with cross trial comparisons etc.
With all due respect this is not Exelexis trial it was conducted by ECOG. My guesses is the press release will follow the presentation on Sunday. I don't understand why you find it difficult to believe that they would not be reporting OS data after all they already disclosed in the abstract the HR was 0.50. They submitted the abstract months ago and were most likly still waiting for events so they could determine the medians of each arms. These facts above and the fact that ASCO selected this as an oral presentation doesn't take a genius to conclude what I have, OS will be reported.
Yes you are correct HR reflects the entire curve and can be reported prior to the median being reached. Given that PFS events where reached back in Oct and given the fact that ASCO chose this as an oral presentation leads me to believe the median for OS has been reached and will be reported.
Yes that's it but this trial has been done for some time now. We know the PFS was positive and we know the HR is 0.50 for OS we just don't know the absolute OS difference. This absolute OS topline data will be reported at ASCO
ECOG E1512 OS results will be reported. Mark my word this is the most important presentation at ASCO for EXEL...,. Oral presentation on Sunday,
As Ive stated previously on another thread this is the study that is a sleeping giant for PPS rise. People need to appreciate this is in EGFRwt pts. That's about 70% of all NSCLC pts. The real question is how to design a pivotal trial. Docetaxel is all but soon to be irrelevant in second line as soon as nivo's approval extends to adeno, So the way I see it the trial needed is Cabo plus or minus Nivo.
Wall Street will not be able to ignore E1512 showing a significant OS over erlotinib in refractory NSCLC. If the absolute OS benefit is similar to docetaxel then this trial is a huge catalyst to pps in my opinion. It also increases the likelihood that Cabo will meet its primary endpoint in RCC.
I don't believe you could use erlotinib as a comparator in this space. Nivo et al are emerging 2nd and 3rd line options pushing docetaxel and erlotinib to later lines. it would be a real question what to use here but I think your going to have compare or combine with immunotherapy.
the real question is what to compare Cabo to in a registration trial. Clearly erlotininib isn't the best choice nor is docetaxel and given that nivo is rapidly moving into 2nd line I think they will need to do a phase I/II with Cabo plus minus Nivo and if good move this to phase iii. With the stated HR of 0.50 and historic OS for this population erlotinib probably in the range of 4mo I'd estimate Cabo arms over 8mo we will see at the oral presentation
Interesting Cabo beat eroltinib along and in combination both showing significantly improved OS with HR about 0.50. So Cabo not only had a PFS advantage which has been known but now has a significant OS advantage over eroltinib. Abstract did not give absolute OS so I assume his will be reported at the oral presentation. IMO this data is a sleeping giant in terms of potential effect on pps. Time will tell I guess.