controlled brain mets and clinical trial - 1288681

Hi Kempten,

What you'll find is that every trial has different entry criteria, although it's fairly common to accept patients with controlled brain mets. You would just need to check with the trial staff for the particular trial in which you have an interest. At the same time, you could ask about their procedures to deal with progression while on the trial, and whether they treat progression in the brain differently than progression in the rest of the body.

I don't know that you can assume that the brain mets will recur during the time you're on the trial. If you're having progression elsewhere, you might not want to pass up an opportunity at a trial drug that may control the disease, based only upon the assumption that brain mets will recur and you'll be dropped from the trial.

JimC
Forum moderator

Hi Kempton.

I just wanted to reiterate Jim's comment that every trial has its own criteria for acceptance and exclusion and you would need to check with trial staff about details. Although my wife does not have brain mets, I noticed when we were looking at clinical trials for my wife that rather than the current or past presence of brain mets themselves, many of the trials exclude patients who require high doses of steroids in the management of the brain mets. But, this is highly dependent on the type of drug and type of trial, so always check with the trial staff. Similarly the criteria for the types and extent of progressions which kick you out of a trial also vary. The trial coordinators were very friendly and helpful during our initial screening meeting in explaining their criteria. They also explained to us that for our trial drug, if it was shown to be working for the cancer my wife could remain on the drug, even after the formal trial was over.

Hi Kempten,

I understand your concern. The problem is that pretty much any treatment regimen crosses the blood brain barrier, but often not at a sufficient concentration to be effective.

If the drug is not approved for lung cancer (or your specific subtype or treatment history), there are two possibilities: One, if the drug is approved for other scenarios, it can be prescribed off-label, and the main question would be whether your insurance would pay for it. Often, if they categorize a drug as investigational, they will refuse coverage, unless your doctor can successfully convince your insurer to cover it based on preliminary evidence of efficacy. If not, self-pay might be an option, albeit an expensive one.

Two, the drug manufacturer may have a compassionate use program approved by the FDA (or other authority if outside the US), in which they will allow access to the drug based on your circumstances. There is a thorough discussion of this subject in this thread: http://cancergrace.org/forums/index.php?topic=6164.0

JimC
Forum moderator

I had an unexpected interruption so Jim commented before I finished but I'll keep it as is:

Hi Kempten,

I'm so sorry to hear you've progressed on tagrisso. It's very possible that the cancer in the brain is completely gone it not return.

A good way to think about it is what would you do if you weren't on a trial and the brain mets recurred. For many trials the answer is the same as if you weren't on a trial and most likely that would be to stop systemic treatment and deal with the brain mets then go back on the systemic drug. However as Jim and scohn have said that depends on the way the trial is set up and to some extent the trial oncologist you're seeing has some leeway into how to manage a situation.

We have a series of video posts on the subject of clinical trials that would be helpful in explaining how they are setup and why.
http://cancergrace.org/cancer-101/2013/01/06/clin-trials-ramalingam-pt-…
http://cancergrace.org/cancer-101/2013/01/18/how-are-clin-trials-develo…
http://cancergrace.org/cancer-101/2013/01/27/ramalingam-clin-trials-pt-…

I hope you don't expect the worst from trials but I certainly understand the need to know how the process works. Not all trials are created equal in design.

Please keep us posted.

Janine

It sounds like you're in great hands and hopefully find an appropriate combo trial. There are trials that are looking at new drugs in combo with lesser understood mutations that appear promising however they are only being given in trials. You won't find an oncologist dana farber or mass gen who will give experimental drugs outside of a trial nor will an insurance company pay, for good reason. See scohn's wife's journey she is on one such combo trial.

Keeping everything crossed for good outcomes!

Hi Kemptom,

I'll ask an oncologist to comment. Your questions are good and timely and probably a moving target. Like you said the added toxicities are a concern.

Janine

You bring up a few excellent questions that I'm happy to provide some information on. To my knowledge, there are no publicly available data on the question of whether adding Tagrisso to chemo after progression on Tagrisso helps as compared to chemotherapy alone. The closest data that we do have are with the same question after 1st generation TKIs (like erlotinib). There, continuation of the TKI improves the response rate (which, in oncology, is defined as the % of patients with shrinkage of at least 30% by a system called RECIST). However, survival was not improved. While the combination was tolerable, there was more rash and diarrhea than with chemo alone. In my practice, I have never done this and so I don't have any knowledge of whether insurance would pay for it.

Dr. Johnson and Dr. Sequist are both world class.

Every trial has different rules. It is pretty new that some trials allow patients to continue on a drug past progression if their doctor feels that its helping them. Very few trials allow patients who stop a drug to later get back on it on trial (although with the immuno trials, we've seen a few exceptions to this).

I do think of progression in the brain differently from progression in the rest of the body. When cancer grows in the non-brain parts of the body, I assume that the cancer has some resistance mechanism. In contrast, when cancer grows only in the brain but is well controlled in the rest of the body, it can be because the drug simply isn't getting into the brain. Outside of trials, I will sometimes radiate the cancer in the brain, then go back to the original drug for the rest of the body. In the case of 1st line EGFR treatment with erlotinib, we even a trial prospectively evaluating this approach.

Hi Kempten,

I don't know how often oncologists are continuing Tagrisso and adding chemo to it, but before the discovery of these third-generation TKI inhibitors, some doctors were adding chemo to Tarceva at the time of significant but not widespread progression. In fact, our oncologist prescribed Tarceva/Alimta when my wife's cancer began to progress on Tarceva, and it seemed to work for a while, without much in terms of additional side effects. Granted, you're adding carboplatin to the mix, but carbo/Alimta in general is one of the best-tolerated platinum doublets around. While the side effects of Tarceva and Tagrisso aren't exactly the same, they are similar enough to think that the combination won't be too toxic for you. Though there is some overlap in terms of digestive tract issues, the side effects of chemo and an EGFR TKI tend to be different, and hopefully you would not find those issues additive from the combination.

As far as insurance, that's hard to say, although both carbo/Alimta and Tagrisso are approved NSCLC agents, so there's a reasonable chance it will be covered. My wife's insurance covered her combination without batting an eyelash, and that was six years ago.

JimC
Forum moderator