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JUST OUT in the @TheLancet
led by @ManniMD1, we ask tough questions to the BOSTON trial investigators
How do the authors justify a grossly unethical control arm?
.... beneath the standard of care when they ran the trial?
https://tinyurl.com/uhun92z7
You won't believe the reply...
led by @ManniMD1, we ask tough questions to the BOSTON trial investigators
How do the authors justify a grossly unethical control arm?
.... beneath the standard of care when they ran the trial?
https://tinyurl.com/uhun92z7
You won't believe the reply...
First, what did we point out
We asked, given the control arm was known to be inferior when they launched the trial... How do they justify it?
We asked, given the control arm was known to be inferior when they launched the trial... How do they justify it?
How do they justify the crossover?
Vd --> Svd.
Potentially for someone first treated with VRd.
There are so many effective drugs such a patient is denied!
Vd --> Svd.
Potentially for someone first treated with VRd.
There are so many effective drugs such a patient is denied!
Their reply
They disagree with our contention that Velcade, dex was an inferior control arm.
Wow
In 2017, when trial launched, no US docs would treat their loved one with velcade dex second line...
They disagree with our contention that Velcade, dex was an inferior control arm.
Wow
In 2017, when trial launched, no US docs would treat their loved one with velcade dex second line...
they say V-d is a standard of care by the 2021 guidelines...
that sounds odd...
lets check those guidelines..
that sounds odd...
lets check those guidelines..
Sure enough it is odd...
It is not a preferred treatment it is 'useful under certain circumstances', which is not exactly a ringing endorsement
but maybe more than we can say for selinexor
It is not a preferred treatment it is 'useful under certain circumstances', which is not exactly a ringing endorsement
but maybe more than we can say for selinexor
They say other contemporary trials used the same sub-standard control arm
is that true? what is ref. 6?
is that true? what is ref. 6?
Optimismm... but
When did they enroll pts?
When did they enroll pts?
OPTIMISMM 2013 - May 2017
BOSTON June 2017 to 2019
So unless they are using a calendar I am not familiar with, since May is before June, the statement is false
BOSTON June 2017 to 2019
So unless they are using a calendar I am not familiar with, since May is before June, the statement is false
They say they tried to isolate the effect of selinexor?
I think this claim is inaccurate.
Seli was already approved, the question was when to use it, not to isolate the effect...
(we will come back to this)
I think this claim is inaccurate.
Seli was already approved, the question was when to use it, not to isolate the effect...
(we will come back to this)
They brag that selinexor allows you to use less bortezomib and replace it
that made me smile because it is revisionist history...
why is selinexor given with less bortezomib, shall we refresh our memories?...
that made me smile because it is revisionist history...
why is selinexor given with less bortezomib, shall we refresh our memories?...
It is because when you did DOSE ESCALATION
you COULD NOT give your drug with that dose of velcade
Now they act as if the reason is a benefit (less velcade), the reason is toxicity... Aaand what does this mean for the claim
'isolate effect'.....
you COULD NOT give your drug with that dose of velcade
Now they act as if the reason is a benefit (less velcade), the reason is toxicity... Aaand what does this mean for the claim
'isolate effect'.....
Ironically, it means that your trial with its subpar control arm did not 'isolate the effect' of selinexor -- not that anyone wanted that-- because you cannot give selinexor on top of the velcade dose used in the control arm
so you alter 2 things now... which means...
so you alter 2 things now... which means...
you could have simply tested SVd against a fair control arm
You know the sort of control arm they were using in BOSTON at the time.
You know the sort of control arm they were using in BOSTON at the time.
I feel bad for all the patients, and especially these patients and this was not US standard of care at the time.
In Short, BOSTON trial was practice changing
It should change our practice of using control arms beneath the standard of care....
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00274-9/fulltext
which we detailed in 2 papers...
It should change our practice of using control arms beneath the standard of care....
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00274-9/fulltext
which we detailed in 2 papers...
It is sad that the US FDA allows this, but after the last 3 days, not surprising
