Anaplastic lymphoma kinase and lung cancer - 1250052

Hello Lynn, Welcome to Grace. I'm very sorry you are dealing with lung cancer but think you will be able to access all the most up to the minute info on ALK and lung cancer here on Grace. We have a very active ALK and ROS community including a thread that is unofficially officially run by member Craig (hope you don't mind my saying so Craig). I have link to it below.

By doing using the words celiac, ALK, and lymphoma in our search engine I didn't get any results. That doesn't mean there isn't anything to say about it I'm just saying I tried to find something relevant already discussed.
I cannot help you with your question but will contact a doctor to comment. You should hear back within a day.

Please check out this thread and join if you think it might be helpful to you or you to someone else.
http://cancergrace.org/topic/alk-or-ros1-nsclc-patient-group/page/3/#po…

Thanks,
Janine
forum moderator

Hi Lynn - Just wanted to add that in the context of lung cancer, it's great news to have the ALK. As I'm sure you already know, it makes you a good candidate for the new drug Xalkori (crizotinib), which is taken as a pill. We've got people here on GRACE who've been taking Xalkori with great success and relatively few side-effects. That might be why you've seen ALK positive NSCLC referred to as a "disease within a disease" - because with Xalkori it offers the promise of longer survival than most lung cancer patients can hope for. Here is a post Dr West wrote when Xalkori was first approved by the FDA last year:
http://cancergrace.org/lung/2011/08/27/alk-inhibitor-xalkori-crizotinib…
I wonder if your lymphoma question was triggered by the Wikipedia entry, which connects the ALK with a number of cancers, including lymphoma?
http://en.wikipedia.org/wiki/Anaplastic_lymphoma_kinase
Mutations operate differently in different kinds of cancer, so if your worry is that you might develop lymphoma as a result of having the ALK, I hope a doctor can reassure you that is not the case.
It sounds as if you might be recently diagnosed, in which case you will find lots of information and support here. Best wishes.

What a horrible year you have had. I am sorry to hear of everything you have been through. Congratulations however on your good results from treatment.
Could I ask what you mean by "it is extremely aggressive in NSCLC patients"? Have you gained the impression that having the ALK rearrangement makes the cancer more aggressive? I don't think that is true at all, and I hope a doctor will confirm this.
If I were in your position, I would gain some reassurance from knowing that if the cancer should recur at some time in the future, there is a targeted therapy out there which can stop it growing for a long time. Xalkori is an amazing drug. What's more, it is not as intrusive as chemotherapy - taking a daily pill makes it possible to lead a relatively normal life. I am sure you will feel better about all this when you have a response from Dr West or one of the other doctors. Very best.

I'm very sorry to hear of all you've gone through. There are some people who say that chemotherapy and EGFR inhibitors are ineffective in patients with an ALK rearrangement, but that's not especially true for chemo. ALK-positive patients may not respond particular well to EGFR inhibitors overall, but their outcome appears pretty similar to what we see in a broader, general NSCLC population other than when they're receiving crizotinib (XALKORI), where they tend to typically have a very good and often long lasting response.

The ALK rearrangement is seen in some kinds of lymphomas, but it isn't related to celiac disease. There are many kinds of lymphoma, and one subtype is associated with celiac disease.

As for the "disease within a disease", I think this refers to it just being a very specific, limited subtype that comprises just 4% of the broader population of advanced NSCLC, and perhaps that it's felt to be the driving force behind the cancer that the people with an ALK-positive NSCLC get.

Good luck. I hope your response continues to last a long time.

-Dr. West

Lynn, I hope Dr West's response has relieved at least some of your worry. Many people here on GRACE know what it is like to be petrified by the prospect of recurrence, so you are not alone by any means. Please come back to us if you need more information, or just for support.

Dear Lynn,

Sorry to hear about your recurrence. I echo all of Dr. West's comments above. I would like to point out that even though ALK + tumors make up only 4-5% of all NSCLC, there has been tremendous research in this particular subset of NSCLC over the last 1-2 years. At our last annual oncology meeting we heard promising results of a new drug, LDK-378 that seems to be the "new and improved" Xalkori. There are several other oral agents that target ALK in clinical trials at centers throughout the US, and we eagerly await the results of those trials.

I hope that this assures you that there are many options for you beyond Xalkori, if you were to need them.

Good luck!

Charu Aggarwal

Yes, there's LD378 and AP26113 and also Chugai CH5424802, all of which are looking promising in the early research results, better than Xalkori. These are so potent that if the mechanism of resistant isn't an ALK-mutation they might still shrink the ALK-driven cancer so much that there's overall improvement until the non-ALK resistance becomes the dominant issue.

So it will also be important for researchers to identify strategies and treatments for other kinds of ALK resistance *and* things that don't depend on a specific driving mutation. For example, immunotherapy approaches (vaccines like Lucanix or Simuvax might help a few people and anti-PD-1 drugs look hopeful for a portion of patients, and other approaches are being researched). And strategies like zapping away spots of resistance using targeted radiation (which studies are starting to suggest might as much as double the useful time of inhibitors drugs in some patients). And don't forget chemo approaches. (Alimta + platinum-based chemo has higher odds of working in never- or light-smokers, and ALK patients tend to be never/light-smokers.)

IMO, the next several years will be an exciting time in cancer research for ALK-driven (and ROS1-driven) lung cancer. Even if much of it becomes a breakthrough too little/too late for us, progress is being made and there's hope of extending our time even though we always need to be prepared for the worst at all times (as all people should anyway). When I came to this forum, I was looking at dim prospects of lasting more than 2 years, but research put me on the ALK/ROS1 track and turned back my clock, making the expiration date stamped on my butt too fuzzy to read but it's not this year. If I draw the short stick, well, I could've been hit by a truck, too, but there's hope of some extra time for us and especially for our ALK successors.

Best hopes,

Craig in PA

Don't get hit by a truck. You're helping people and you are a fantastic motivating presence.

Just wanted to say that my center is working on activating the trial for the Chugai 2nd generation ALK inhibitor, if someone here finds themselves needing that option for acquired resistance in the next few months. I don't know the exact timeline (it involves prayer to the contract and regulatory committee gods), but we're trying to get that expedited and available.

-Dr. West

I am sorry to hear about your lung cancer diagnosis. It is good to hear that you were able to complete the surgery, chemotherapy, and radiation without many problems. It sounds like you have received aggressive and appropriate therapy for your stage IIIA lung cancer. Indeed some studies suggest that ALK+ patients experience greater benefit from Alimta-based chemotherapy (including the recently reported PROFILE 1007 study). See below for a previous discussion on Alimta for ALK+ lung cancer patients:
cancergrace.org/lung/2011/02/26/alimta-for-alk-rearrangment/

I understand your concern for recurrence and the stress related to waiting for the follow-up scan results can be very difficult. Currently, crizotinib (Xalkori) has no proven role in stage I-III lung cancer, but would be a very good therapy option if your cancer were to unfortunately recur. There are also many other drugs that are currently in development for ALK+ lung cancer so that hopefully there will be many more options in the future. I agree with comments above that ALK+ lung cancer is a small subset of all lung cancer patients and that is why it has been referred to as a "disease within a disease." It is still unclear what causes to ALK+ lung cancer. It is also not clear that ALK+ lung cancer is any more aggressive than other types of lung cancer and as with any type of cancer there is a great variability from patient to patient in the "aggressiveness" of their tumor.

Robert C. Doebele, MD, PhD
Medical Oncologist
Views expressed here represent my opinion, not those of GRACE or the University of Colorado. This information does not constitute medical advice and is intended to supplement and not replace medical information provided by your doctor.

Regarding that first point:

As I understood it, Dr. Shaw's research tested that hypothesis directly and found that Alimta did not favor ALK+ patients, but rather favored never-smokers (specifically when in combo with a platinum-based chemo, not used alone, if I recall correctly):
http://annonc.oxfordjournals.org/content/early/2012/08/09/annonc.mds242
Of course ALK+ are much more likely to be never-smokers, so there is a plausible indirect connection.

And she also reported that the PROFILE 1007 study found Xalkori to be superior to Alimta for ALK+ patients. (I think I remembering hearing this was an important issue in some countries where they were considering requiring patients try Alimta before trying Xalkori.)
http://www.oncologystat.com/news/Crizotinib_Changes_Practice_for_Advanc…

Best hopes,

Craig

I don't doubt that XALKORI (crizotinib) is superior to Alimta (pemetrexed) for ALK rearrangement-positive patients. However, among chemo agents, Alimta is a generally well tolerated drug that is at least as effective, pound for pound, as many alternatives, particularly for an adenocarcinoma, which is what most ALK-positive patients have. So my take-home conclusion is not that Alimta is better than XALKORI for an ALK-positive patient, but if you're limited to chemo-based options for a given patient at a given time, Alimta is a strong one for this population.

-Dr. West

Dr.West

I saw a MSKCC doctor prefers CH5424802 more than LDK378.
I could not find why from website, because it seems most of people said LDK378 is good one. I want to know the slight difference.

If two experimental drugs both seem very promising, would a medical center have a bias toward the one that they are participating in rather than send the patients elsewhere?
http://www.clinicaltrials.gov/ct2/results?term=LDK378+lung&Search=Search

Best hopes,

Craig

Currently LDK378, CH5424802, and AP26113 are next generation ALK inhibitors that are currently in phase I clinical trials. LDK378 seems to have accrued the most patients thus far (based on presentations at ESMO 2012). All three drugs have provided some evidence for tumor response in ALK+ patients with crizotinib resistance and all three drugs have shown some anecdotal activity in shrinking brain mets. I think it is much too early to know which drug is best in terms of effectiveness or safety.

I didn't know all 3 had case reports of brain met activity -- good to hear.

I might be remembering incorrectly, but I thought the early data that was shared was for Xalkori-naïve patients in some cases and Xalkori-resistant ones in others, so you can't directly compare the % odds of benefit.

To elaborate on the safety point: I don't think optimal doses for effectiveness vs. safety have been found (e.g., may need a high dose to improve control over new variants that might arise but high doses increase side-effect troubles, and we haven't seen any early data on that yet). Or maybe LDK378 is further along in that regard?

Hypothetically, one might want to know which specific type of Xalkori resistance a person has before throwing a particular drug at it which might or might not be the best for that. As a practical matter, though, that's not likely to be considered until there's a lot more experience about which drugs work best for which (unless it's a non-ALK / non-ROS1 mutation or amplification causing the resistance). At this point though, in terms of early effectiveness, all three seem promising for a large % of patients from what's been disclosed so far.

Best hopes,

Craig

LDK378 and AP26113 reported data from both crizotinib-naive and crizotinib-treated patients whereas CH5424802 reported data only on crizotinib-naive. But again, all the data is relatively early.