Friday, May 19, 2017

ASCO: Copanlisib for Follicular Lymphoma

It's that time of year! ASCO abstracts are out!

In early June every year, the American Society of Clinical Oncology (ASCO) holds its annual meeting. It's a big meeting, meant for clinical oncologists -- the people that we see in their offices -- so the research that gets presented is usually pretty practical. It's a meeting for oncologists of all specialties, so there aren't always as many Follicular Lymphoma presentations as there are at a conference like ASH, which focuses on blood cancers. But because it's a big meeting, the presentations are usually significant.

I like to preview some of the more interesting sessions, looking at the abstracts for stuff that gets me excited. Once the conference happens, pharmaceutical companies and universities will start to send out press releases, bragging about their stuff (good clinical trial results, for example). Sometimes, the news is so good, they start talking about it weeks before the meeting.

And that happened this year (sort of). There will be a session called "Copanlisib in Patients with Relapsed or Refractory Follicular Lymphoma." That's good stuff, but even better is the news that the FDA has granted Priority Review to Copanlisib, based on the clinical trial results that are going to be discussed at ASCO.

So let's look at the ASCO abstract first. Copanlisib is a PI3K inhibitor.There are lots of different inhibitors out there for cancer, and for FL. Haters hate, as they say, and inhibitors inhibit -- they keep something important from happening in a cell. Different inhibitors focus on different things.

PI3K inhibitors focus on the PI3K enzyme, which is needed for a cell to do some important things like grow normally. When there is a problem with the pathway, the cell grows uncontrollably (resulting in cancer). By inhibiting the enzyme, the uncontrollable growth is stopped.

(There's more to it than that -- it involves something called the PI3K/AKT/mTOR pathway, which is really important to cell growth. But we'll just keep it simple. Let's all agree that this is a really important thing to target with an inhibitor.)

Another really important thing about Copanlisib that makes this a big deal is that PI3K actually comes in a few different forms (called isotopes). Most inhibitors only target one of those forms -- Copanlisib targets two of them.

So, the ASCO presentation is going to discuss the results of a phase II clinical trial. A total of 141 patients were in the trial, but the 104 with Follicular Lymphoma are the real focus. These patients were relapsed/refractory (their last treatment didn't work, or stopped working), and had at least 2 prior treatments.

The results were impressive -- Overall Response was 58.7% (14.4 % had a Complete Response and 44.2% had a Partial Response), with another 33.7% having stable disease. The median duration of response was just over 1 year.

Side effects were "manageable," and included diarrhea, reduced neutrophils, fever and fatigue. There were 6 deaths in the group, with "3 attributed to Copanlisib" (a lung infection, a respiratory failure, and a blood clot).

Even with those problems, the researchers point out that Copanlisib did not show some of the problems that other PI3K inhibitors have shown, including infections, colitis (inflammation of the colon), and hepatic enzymopathy (problems with liver enzymes).

Which brings us to the big news about the FDA granting Copanlisib a Priority Review designation. This designation means that the FDA plans to take action within six months (a regular review takes 10 months). Getting the designation means that the FDA thinks it is important that the treatment becomes available quickly, because it's doing something that other treatments aren't doing.

In this case, it seems like the combination of effectiveness and safety is what makes this a better option than some others that are available. I'm guessing that the lack of problems that get seen in other PI3K inhibitors was a big factor.

The question that I had (and that you might have too) is something like "Wait -- didn't it say that 3 people died?" Yes, and that does seem to be downplayed in the reports that I have seen about the FDA approval (though it is certainly mentioned in the ASCO abstract).

It's important to remember that this is a fairly narrow FDA approval, and that is still pending -- it is only for FL patients with refractory/relapsed disease, and who have had at least 2 prior treatments. In other words, this is potentially being approved for patients who are running out of options. So the deaths among trial participants might not be quite as significant. If this were an approval for a first-line treatment, there would be much more attention paid to those unfortunate "adverse events."

So, there's your first ASCO preview. I'll keep looking at the abstracts for more interesting news. Stay tuned.


Alecia Madonado said...
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Anonymous said...

Anyone considering a PI3K treatment for fNHL should compare the effectiveness, duration, and safety profile of Copanlisib (IV) with Idelalisib (pill).

Lymphomaniac said...

Anonymous: Absolutely. Ideally, in a conversation with your oncologist, and with enough knowledge for it to be an informed conversation.

Unknown said...

Idelalisib, Delta study (Gopal et al, NEJM, 2014, DOI: 10.1056/NEJMoa1314583) used for approval in iNHL: "Eleven deaths occurred while the patient was receiving the study drug or within 30 days after the last dose." They just don't tell if These deaths were drug-related or not.