Ipilimumab (Yervoy - anti-CLTA4) a type of immunotherapy, was FDA approved for Stage IV melanoma in 2011 and as an adjuvant treatment for Stage III patients in 2015. Despite its significant side effect profile, the limitations of its 15% response rate, time has proven the durability of many of those responses. In whatever light you see it now...it was an unbelievable boon to those of us with melanoma in the years before 2011 when our choices were limited to conventional chemo (known to be dismally ineffective against melanoma), IL-2 or interferon.
As such, with the advent of the anti-PD-1 products Nivolumab/Opdivo and Pembrolizumab/Keytruda with their response rates of 40% and decreased incidence of adverse effects the the role of ipi is....undefined, shall we say...except by the FDA, who in their wisdom have ordained the following:
1. Stage IV melanoma patients may be given the ipi/nivo combo (also FDA approved in 2015)...in which ipi is dosed at 3mg/kg...for a response rate of 50+%.
2. Stage IV patients shall be given ipi, if they desire or if they have failed other things...alone at a dose of 3mg/kg.
3. Stage III patients may use ipi (but not the anti-PD-1 products nor the ipi/nivo combo) at a dose of 10mg/kg.
So...here's the question(s)... Why give ipi at a greater dosage for Stage III folks than for Stage IV folks? Why can Stage III folks not have access to the other options? Which dose of ipi is better?
To the first two pregunta's....the answer is simply: that is how the trials with the meds in question were set up when they were submitted for FDA approval. Can the FDA not extrapolate between various studies? No! Can the FDA use common sense? No. I could go on....but... As to the last question...which dose is better??? Most experts and studies have indicated that despite the sad fact that folks who have already taken ipi respond less well to anti-PD-1 later should they need it [ Sequential nivo then ipi = ORR of 41%. Ipi followed by nivo = ORR of 20%!!!! FDA! Are you listening??????? ] the 3 mg/kg dose provides almost the same responses as the 10 mg/kg dose with a much lower side effect profile...though Weber has admitted that should you be able to tolerate the 10 mg/kg dose the response ARE actually, a little better.
However, I was a little concerned when I read and posted this study: Ipi - 3mg vs 10mg/kg - Increased OS with increased SE on 10!
Now, there is this from ASCO comparing ipi at 3mg/kg to 10mg/kg in advanced melanoma...
(Oh, and of course, if Kirkwood has his name on it...interferon will be involved...even if it does nothing more than torture innocent ratties...even if it has nothing whatsoever reportable to offer...it is a horse he is going to ride until he drops. Please dear God, never, ever, ever, ever let us be THAT person. The person who is unwilling to admit error. Unwilling to move on with the times. Unwilling to stop the suffering of others when all he would have to say is...I was wrong.)
|Grade 3+ ae's||ipi 10 (%)||ipi 3 (%)|
Sorry. Interferon rant over...for now.... Ipi 3 vs 10 - equal success. More side effects with 10. FDA....are you listening?????? - c
PS: The Edster shared this link where Dr. Weber addresses his Top 5 important picks from ASCO, including this one. See his review here: http://www.medscape.com/viewarticle/880602