An interesting therapy comparison has come out in recent days, worth a mention to those who want to update their scorecards.
In this corner, weighing in at a zillion tons, breathing enough fire to melt Mt. Fuji, is our current champion, the Godzilla of CLL clemotherapy -- FCR (Fludarabine, Cyclophosphomide, and Rituximab, Genentech's long-standing anti-CD20 monoclonal antibody).
And in this corner, causing the earth to shake with the whip of its newly-minted tail, is the Mechagodzilla of CLL chemotherapy -- FCA (Fludarabine, Cyclophosphamide, and Arzerra — aka ofatumumbab, Genmab’s competing anti-CD20 monoclonal that is now very close to approval by the FDA).
We all know that the loser is going to be Tokyo. And the winner is . . .
Both, or neither, depending on how you look at it!
Genmab just announced the Phase II results of a trial of 61 chemo-naive patients who were treated with FCA. Those who received the largest dose of ofatumumab (which also used to be known as HuMax-CD20) got a 50% complete response rate as measured by the 1996 National Cancer Institute CLL guidelines. (According to Genmab, the CR rate was 32% in patients who received 500 mg of ofatumumab and 50% in those who received 1000 mg. The overall response rate was 77% in the 500 mg group and a slightly lower -- go figure! -- 73% in the 1000 mg treatment group.) Obviously, the study is ongoing, so we don’t have any idea how long those “complete responses” will last.
Compare Genmab's results to those reported by the respected German CLL8 study group in 2008 in a trial of 817 patients randomized to receive either FCR or FC. The FCR group received a 52% CR rate using the 1996 NCI criteria. Assuming some basic equivalency between the studies, that’s a two percent difference, statistically insignificant.
Progression-free survival in the German study was 76.6% at 2 years in the FCR arm and 62.3% in the FC arm. But the difference for overall survival was not significant (91% v 88% at 2 years).
(MD Anderson has been providing its own ongoing retrospective, non-randomized information that paints a rosier picture of FCR; it is worth noting Dr. Terry Hamblin's comments here.)
Which brings us again to the perennial question: What's the "best" choice for your first therapy, and how does that impact what you do after relapse, when it's time for that second act that we often tend not to think about?
In my case, having pretty much used up Rituxan, it’s going to involve some Arzerra in the hope that it works better as a second-act agent, which it does appear to do. It is now being considered for FDA approval for those who are considered double-refractory to fludarabine and alemtuzumab (Campath), neither of which I have had yet -- but neither of which, the more I use chemotherapy of any kind, is going to work as well as it would have had it been my first choice out of the box.
So welcome to the boxed-in world we CLL patients live in. What do you chose for your first act? How does that impact what you choose for your second? (And, transplant planners, how do those choices impact that third and probably final -- and I mean "final" in the hopeful "cure" sense -- act?)
Which brings us to another bit of recently-reported information, floating around the air like Mothra:
“First-line fludarabine not superior to chlorambucil in older CLL patients”
In a study of patients over age 65, the German CLL Study Group randomized 95 patients between fludarabine and chlorambucil.
Progression-free survival was similar in the fludarabine group (19 months) and the chlorambucil group (18 months); however, clinical significance was not reached. Overall survival was also similar between the two groups (46 months vs. 64 months), but again, clinical significance was not reached.
The bottom line is that fludarabine provided a more robust response (as well as more bone marrow toxicity) but in the end that deeper remission didn’t mean the patients were living any longer, at least as of this writing. Keep in mind the OS non-difference between FCR and FC as reported by the German CLL8 group.
Of course, the trick is to track these things over a much longer time period, to see how overall survival of Regimen A vs. Regimen B goes on year after year after year.
Unless, of course, your CLL isn't giving you a decade or two to watch all the data dribble in.
Then you have to pick your monster and place your bet.
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