Brain scans in CRIZOTNIB patients - 1263356

Hello seesken,

When asked about frequency of brain MRIs while on crizotinib, as well as whether to add a chemo agent to crizotinib in an effort to prevent brain mets, Dr. West stated:

"Unfortunately, the evidence-based best answer to both of your questions is “we have no idea“; any other answer is just a vague judgment based on our biases.

It’s not that these aren’t good questions, but these questions have never been studied. There is no evidence that there is anything in this situation that can be done to postpone brain metastases. If brain metastases do occur, there is no evidence that doing brain scans regularly leads to any better outcomes than finding them based on symptoms. It does lead to more brain scans and more anxiety, but not necessarily better outcomes." - http://cancergrace.org/topic/scan-frequency-while-on-crizotinib#post-12…

On the other hand, in the same thread Dr. Doebele stated a contrary practice:

"We are now routinely screening ALK+ patients by brain MRI approximately every 6 months while on crizotinib. There is little data on crizotinib brain penetration (although a famous case report suggests it was very low in one patient), but we know that this can be variable from patient to patient."

While practices may vary, as Dr. West stated there is insufficient evidence that finding brain mets earlier through routine scanning improves outcomes. As Dr. Weiss has stated:

“I typically acquire an MRI at diagnosis, then again if symptoms suggest. Some oncologists obtain more regular MRIs. I have no objection to this, but am not convinced that it improves actual patient outcomes compared to having a low threshold to get MRI once symptoms develop.” – http://cancergrace.org/lung/topic/should-brain-mri-be-done-even-in-abse…

JimC
Forum moderator

I'll say that there is a growing sense that it is appropriate, though certainly not mandatory, to do surveillance brain MRIs in patients doing well on XALKORI (crizotinib). Such patients often do well overall for a very long time (long enough that they are more subject to risk of brain metastases over time than patients without a driver mutation, who don't tend to have as favorable a prognosis), and XALKORI doesn't get into the brain to any meaningful extent (seemingly unlike the second generation ALK inhibitors like ceritinib, alectinib, and AP26113, which have all been documented to lead to responses of brain metastases). And yes, there is a significant risk of brain first/brain only progression on XALKORI, for which many and I would say most experts would favor radiation to brain mets and then continuing the XALKORI in the face of very good control of disease extracranially (outside of the brain).

So while I stand by my prior statement that there was not and still is not evidence that outcomes are improved by doing surveillance brain MRIs, and I do not favor them in general management of advanced NSCLC patients who don't have a history of brain metastases, I am increasingly inclined to favor surveillance brain MRI scans in patients with an ALK rearrangement and doing well on XAKORI. I would just add the caveat that this shouldn't be a dogmatic stance, in the absence of actual evidence that such surveillance leads to better outcomes.

Good luck.

-Dr. West

Hi Simone,

There are conflicting opinions among experts on the question of stopping Xalkori (crizotinib) during WBR. As Dr. West has said, that disagreement

"...is a reflection on the absence of any actual data to speak to this question. We do tend to be very cautious about risks when the brain is involved. However, the available data (very limited) suggests that very, very little XALKORI (crizotinib) gets into the central nervous system, so there’s good reason to think that it should be safe. Still, there’s definitely no standards or recommendations to make, given the absence of any real evidence to answer your question. Instead, we need to just rely on our best judgment." - http://cancergrace.org/topic/xalkori-during-wbr#post-1260600

As far as whether progression in the brain should warrant a change of treatment, Dr. West has stated the general opinion that "...the radiation will treat the disease in the brain, and the crizotinib will continue to treat the disease outside of the brain." - http://cancergrace.org/topic/crizotinib-after-wbr-in-treating-brain-met…

JimC
Forum moderator

Exactly right...Patients can often do well on crizotinib for many months and sometimes even a year or years after radiation to treat brain metastases. Because crizotinib isn't reaching the cancer in the brain, it's not really that the cancer has become resistant to crizotinib. The cancer can potentially continue to be treated effectively by crizotinib wherever it can reach, and radiation can potentially mop up the rest.

As for taking a break from the crizotinib and the potential for flare, I'm afraid that too many patients are becoming apoplectic with fear about a flare reaction. While it's possible for cancer to progress more rapidly on a break from a targeted therapy, it's very commonly recommended and needed to take time off for side effects, and a few weeks of a break is rarely a major problem. It is often necessary to keep people able to continue these treatments safely. I think some of the discussions of flare reaction really overstate the frequency and anticipated severity: it's not that people suddenly just explode into a million pieces after missing two days of an EGFR inhibitor or crizotinib, which is what it sounds like people are expecting. It just that it's uncommon to rare, but possible, to have an accelerated progression of the disease off of it.

So what does this mean? You aren't throwing the crizotinib down the toilet (or perhaps the loo, in your part of the world). You can always resume it if cancer-related symptoms are clearly escalating quickly. I think if you know to be aware and can be in communication with the doctor, you're in great shape. I personally think it's a fine idea to hold the targeted therapy with concurrent brain radiation, and then you can potentially just start it again if needed. If a person goes a week or two off the oral therapy during the first 1-2 weeks of brain radiation, that at least minimizes the overlap and potential harmful interaction of the medication with WBR.

Good luck

-Dr. West

I have a question with reference to Dr. West's remark in the above post: " I think if you know to be aware and can be in communication with the doctor, you’re in great shape. I personally think it’s a fine idea to hold the targeted therapy with concurrent brain radiation, and then you can potentially just start it again if needed. If a person goes a week or two off the oral therapy during the first 1-2 weeks of brain radiation, that at least minimizes the overlap and potential harmful interaction of the medication with WBR. "
Dr. West's remarks were in May 2014, that was 1 1/2 years ago....are there any more current or new data regarding holding targeted therapy during radiation? Also, in this thread he is referring to the topic of whole brain radiation (WBR). In a previous post, I had inquired about my upcoming scheduled lung tumor radiation, and whether it was still (1 1/2 years later) of the opinion that it's ok to hold off the crizotinib for 2-3 weeks while having "lung" radiation, i.e., no concern regarding flare. So, does it matter which "body part" is being radiated whether or not it's ok to hold off the crizotinib?

Hi Southsidegirl, If the radiation is for a single or so spots stereotactic radiation is being used by some oncologists, including Dr. Weiss. He states in a the video linked below at around the 15 to 16 minute mark and then again at the end that he radiates single spots that come up during an otherwise good response to TKIs then begins the tki again after, suggesting that it's stopped for the days around the ablation. http://cancergrace.org/lung/2014/10/08/ar_forum_after_1st_line_targeted…

I hope that helps.
Janine

Thank you Janine. Your work here is so valuable and appreciated.