When Trials Don't Work Out

I've been thinking a lot about a comment that an anonymous reader made on my last post. The post looked at some history of Follicular Lymphoma, and the comment pointed out that Rituxan by itself had decent results (and I am one of those positive results, as you probably know). But over time, Rituxan was found to be a superstar because it was used in combination with other treatments, and made those treatments better.

So the comment provided a reminder that I very much appreciate: a single-agent treatment that does just OK by itself may have a great life afterwards. Combinations of treatments are often much more effective, and most newer treatments that are working their way up the clinical trial ladder are being tested in a bunch of different combinations to figure out the best way to use them.

Lenalidomide is a good example. It does OK for FL by itself, but combined with Rituxan to create R-Squared, and its results are about as good as chemo + Rituxan.

But there are lots of combinations that are tried that we never hear about. They might make it to a phase 2 trial, and then the results show that it's not as effective as current treatments, or maybe the side effects are too much (which can be a danger with combinations, since two or three treatments could potentially mean two or three times the side effects, though that doesn't always happen).

And there's really no incentive for the people running a trial to publicize the results of a failed trial. They don't need the negative publicity, after all. And the logic is that a failed trial isn't really going to help patients, so there's no point in making the results known.

But is that really the case? There might be something to be learned from failed trials. As a patient, I want to know what kinds of side effects, for example, are happening with some combinations. I like the Big Picture. I've kind of made a career out of cleaning up messes -- my own and other people's -- so I appreciate it when people are honest about failures.

And that's why I liked this article published about a month ago in Clinical Cancer Research: "A 3-Arm Randomized Phase II Study of Bendamustine/Rituximab with Bortezomib Induction or Lenalidomide Continuation in Untreated Follicular Lymphoma: ECOG-ACRIN E2408."

The study looked at Follicular Lymphoma patients who were getting their first treatment (Bendamustine + Rituxan), and then put into three groups: one received Rituxan Maintenance, the second got Bortezomib (Velcade) and then Rituximab Maintenance, and  the third got Lenalidomide and then Rituxan Maintenance.

Results were just OK. The gal was to improve on BR + Maintenance, and adding either Velcade or Lenalidomide didn't significantly improve effectiveness, or reduce side effects (not surprising, when a new treatment is added). I have only seen the abstract, so I can't comment on details of the safety, but the closing of the abstract is pretty clear: "Conclusions: Altogether, neither bortezomib added to BR induction nor lenalidomide added to rituximab maintenance immediately post-BR induction are recommended in untreated FL."

As I said, I appreciate researchers being willing to talk about failure. They can certainly learn a lot, and perhaps we as patients can learn something, too.  One of the questions we will all have to ask at some point is how much we are willing to balance effectiveness and safety. Are we willing to get more months or years between treatments if it means a loss of Quality of Life? How much? In what ways?

To me, even reading about failures brings up those questions, and helps prepare me for the choices I'll need to make some day, even if they won't involve these particular combinations. That's a good thing.