Obinutuzumab vs Rituxan

The New England Journal of Medicine published an article yesterday on the results of the GALLIUM study that compared Obinutuzumab and Rituxan as part of an initial treatment for Follicular Lymphoma. Obinutuzumab came out ahead.

Or did it?

Obinutuzumab was in the news at the end of August, when it was given priority review by the FDA. The review will also be based on the GALLIUM trial results. Obinutuzumab is similar to Rituxan, in that they are both monoclonal antibodies that target the CD20 protein on B cells. But Obinutuzumab  is considered a possible improvement over Rituxan, because it was created differently, to target B cells better, and to cut down on some of the side effects that come with Rituxan's being made from mouse cells (instead of Obinutuzumab's human cells).

The NEJM actually provides a really helpful video that explains the results of the trial. As shown in the video and the article, the GALLIUM study looked at how effective and how safe Obinutuzumab was when compared to Rituxan in FL patients who had not yet received any treatment. The trial involved 1202 patients. Half of them (601) were given chemotherapy + Obinutuzumab, while the other half was given chemo + Rituxan. The chemo could have been Bendamustine, CHOP, or CVP. Patients who had a Complete Response or Partial Response were then given maintenance treatment for up to 2 years (361 for Obinutuzumab and 341 for Rituxan, or an 88.5% Response Rate for Obinutuzumab and 86.9% for Rituxan).

As you can see, there were slightly more patients who had a Response from Obinutuzumab + chemo than Rituxan + chemo. The study was stopped after almost 3 years when it was clear that Obinutuzumab had a better Progression Free Survival rate for 3 years -- 80%, vs. 73.3% for Rituxan. That number is considered significant enough to say that Obinutuzumab is more effective that Rituxan.

This is one of those stories that's getting lots of play in the oncology community. Rituxan has been around for 20 years, and there have been a bunch of attempts to find something that does the same job, but in a better way. Lots of stories online are suggesting that Obinutuzumab has done that.

But then, there are a few more stories that are looking at a second piece in the NEJM, an editorial called "Which Anti-CD20 Antibody is Better in Follicular Lymphoma?" In it, the authors raise some questions that should be raised, and that should make the "Obinutuzumab is better than Rituxan!" article writers slow down a bit. Not many of them did. Medscape was one -- their article reporting on the research is called "Obinutuzumab vs Rituximab in FL: 'Too Close to Call'."

The Medscape article points out some problems with the study that might make the results a little less simple than it might seem. The PFS is significant -- about 7% better for Obinutuzumab.

But there are some problems, too, as the editorial (and the Medscape article) point out.

For example, there is a dosage difference. Patients who received Obinutuzumab had a dose almost 3 times higher than the Rituxan dose. Those are both standard doses for the two, but it raises the question, if the two treatments are generally the same thing, would a higher dose for Rituxan have given better results?

Also, the Obinutuzumab had a higher incidence of adverse events -- things like low blood cell counts, nerve issues, infections, and infusion-related reactions. All of them were more frequent (for some adverse events, twice as frequent) in Obinutuzumab as in Rituxan. That raises the question -- if there is a higher Progression Free Survival, is it enough to make it worth the higher risk of adverse events?

Finally, the editorial authors point out that, while PFS is higher, there is no Overall Survival benefit. So people might go longer before they need another treatment, but they don't live longer as a result of taking Obinutuzumab instead of Rituxan. (I think, though, that's it's too early to measure that statistic.)

The Medscape article also looks back at the ASH session last year that first reported these results of the GALLIUM trial, that showed problems with Bendamustine and Obinutuzumab (and Bendamustine alone).

The Medscape article ends with some interviews with oncologists about whether or not Obinutuzumab will replace Rituxan. The responses were mixed. I can see why -- the study does raise some questions. And, as one doctor points out, the potential FDA approval will be for this very specific course of treatment -- Obinutuzumab plus chemo, followed by Obinutuzumab maintenance. That might not be the best choice for everyone.

My sense is, human nature being what it is, many doctors will continue to stick with what they know, and that means using Rituxan. And my guess (and it's only a guess) is that it will remain that way until there is a really big improvement in the numbers.

And finally, there is a lesson here for us as patients -- a reminder, really. Online stories about cancer are meant to be read, and that means sometimes making them sound better than they are. Most stories about this study didn't bother with the editorial, and the questions it raised. We need to all be careful (me included) to think carefully about what we see, and to make sure we're getting the full story.

Staying informed is the best way to have a voice in our treatment.