Unsuccessful Trial: Ibrutinib + Chemo

I'm finished looking at ASCO presentations, so let's move on to all of the stuff I haven't been able to look at from the last month or so.

The first one is a failure! A clinical trial that wasn't successful. We don't see many of these, even though about 90% of cancer treatments that begin the clinical trial process never get approved. Most of the failures aren't presented at conferences or get published in journals. Which is too bad, because we can learn a lot from failures. (In fact, when I was younger, I kind of made a career out of messing up and then letting everyone know what I learned. It was really effective, and bought me some time until I knew what I was doing.)

The research I'm talking about here was presented last month at the 17th Annual International Conference on Malignant Lymphoma is Lugano, Switzerland, called "Ibrutinib plus BR or R-CHOP in previously treated patients with follicular or marginal zone lymphoma: the phase 3 SELENE study." (I'm getting my information from a write-up from OncLive).

The study looked at the results of a phase 3 trial that compared Ibrutinib plus chemotherapy (either B-R or R-CHOP) against the standard of care (chemo) in FL patients who had already had treatment. Ibrutinib is a BTK inhibitor. BTK is Bruton's Tyrosine Kinase, a protein that is an important part of the pathway that controls B cells (the immune cell that becomes problematic in Follicular Lymphoma and other B cell cancers). So by inhibiting, or stopping, BTK, Ibrutinib helps control the cancer. Ibrutinib has been approved for treatment for several B cell blood cancers, but it hasn't been successful in treating Follicualr Lymphoma.

So maybe it's not a surprise that this trial ultimately didn't work out. 

The phase 3 study came about because the phase 2 study of Ibrutinib alone was successful. In that study, the combo had a response rate of 21% and a median response that lasted 19.4 months for FL patients, with better numbers for MZL, another blood cancer. The numbers were good enough to move on to the phase 3 trial (especially for MZL patients).

For the phase 3 study, the researchers added chemotherapy to see if the FL numbers would approve. To do the direct comparison between Ibrutinib + chemo and chemo alone, 403 patients were put into two groups, each one receiving one of the regiments. 

The numbers were actually good for the Ibrutinib group -- just not good enough. For the Ibrutinib group, the response rate was 91.6%, including 55% Complete Response. In the chemo group, the rsponse rate was 90.5%, with 50.2% CR.

The problem came with Progession Free Survival. There was no statistically significant difference between the groups. 

Safety was also an issue. Whuile no new side effects popped up for the Ibrutinib group, there were a larger number of patients in that group than in the chemo group that had serious side effects, and more patients in the Ibrutinib group had to reduce their dose, or stop it all together, because of side effects.

This isn't surprising, either; combination treatments often have more side effects, since there are more different treatments being used at once. 

The researchers still think that this combination could be useful for certain populations within Follicular Lymphoma, and it sounds like they are going to explore that some more.

So what is the lesson learned? Well, the obvious one is that Ibrutinib still doesn't seem to be a viable treatment for FL, though there are still some trials being conducted that might prove that wrong. And there are also some other BTK inhibitors out there that are a little different from Ibrutinib, which has been a very successful treatment for CLL, Mantle Cell, and other lymphomas. 

We'll see how things go. More research soon.