ALK or ROS1 NSCLC Patient Group

Portal Forums Lung/Thoracic Cancer Patient/User Groups ALK or ROS1 NSCLC Patient Group

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September 29, 2014 at 4:33 pm  #1266199    

Craig

(… continuing …)

My notes on the article:

1. 72% response rate + stability in almost all others

2. Almost everyone with a ROS1 fusion had at least some shrinkage on Xalkori (crizotinib)

3. Median duration is projected to be 17.6 months! (Yes, Xalkori seems even better for ROS1 than it is for ALK)

4. 2/3 of study participants are still in the study (i.e., still working for them)

5. The ROS1 fusion partner gene varied: 44% CD74, then small numbers of SDC4, EZR, SLC34A2, TPM3, LIMA1, MSN
(Mine is one of the rare ones on the end.)

6. There was no obvious statistically correlation between particular ROS1 fusion partner and duration of benefit.
(Looking at the graph has me suspicious that SDC4 might turn out to have shorter than average duration and some of the rarer ones might have longer, but the number of patients are far too small to draw any statistically valid correlations.)

(continued . . .)


- Stage IV never-smoker ROS1-driven m-BAC indolent adenocarcinoma
– Dr. Alice Shaw’s Xalkori (crizotinib)-for-ROS1 trial @ MGH, Boston (5 yrs)
– Currently carboplatin + pemetrexed (Nov 2016+)

September 29, 2014 at 4:38 pm  #1266201    

Craig

(… continuing …)

7. The discussion section elaborates on duration of response and PFS (progression free survival):
7a. for ALK 49.1 week (11.4 mo) duration of response & 9.7 month PFS;
7b. for ROS1 75.9 weeks (17.6 months) & 19.2 month PFS
(It does not make sense to me that PFS would be longer than the duration for ROS1 yet shorter for ALK. It might mean that there’s a good number of ROS1 patients labeled as merely “stable” [less than 30% shrinkage] who remained stable for even longer than the average ROS1 patient who had a more dramatic shrinkage “response,” although that seems counter-intuitive so I could be mistaken.)

8. Most likely reason for longer benefit to ROS1 than ALK is simply that Xalkori is more potent for ROS1 than ALK (binds to active site better)

9. Mechanisms of resistance that emerge after Xalkori: secondary mutation to ROS1 making it resistant, bypass via EGFR activation. Of course others might be identified in the future as work on this subject is early.

10. Trials will be needed to determine whether more potent ROS1 inhibitors will offer a sequential therapy benefit.

As a ROS1+ patient on Xalkori (and one of the first dozen in the Xalkori-for-ROS1 trial) I am grateful to all the researchers (rock stars) and fellow patients (heroes) who contributed to this research, as well as Pfizer (esp. their lead drug designer Jean Cui) for this research and the creation of this drug that has extended the lives of so many ALK and ROS1 patients.

Best hopes,

Craig in PA


- Stage IV never-smoker ROS1-driven m-BAC indolent adenocarcinoma
– Dr. Alice Shaw’s Xalkori (crizotinib)-for-ROS1 trial @ MGH, Boston (5 yrs)
– Currently carboplatin + pemetrexed (Nov 2016+)

September 29, 2014 at 9:18 pm  #1266216    
Dr West
Dr West

Craig,

Thanks for this summary. I know of nobody in this community, myself included, more knowledgeable about the state of the science of ROS1 and potentially ALK.

I think it would be helpful to have this information summarized in a post form, just so it may be easier to search for and print, and without the character limit. I would be happy to have you as the author. I can do it, but I’d just be plagiarizing you. You deserve to be recognized as the expert.

-Dr. West

October 9, 2014 at 3:05 pm  #1266403    

cloeginger

Thank you for this helpful information. I have a question about ceritinib. I have ALK-positive metastatic lung cancer diagnosed in January 2014. I began taking ceritinib in August after the disease progressed while on Crizotinib, and have had a good response, with reduction in the number and size of lesions in my liver and in the brain. However I am finding ceritinib a difficult drug to tolerate. I have had pretty GI side effects, mainly cramps, diarrhea and loss of appetite despite dose reduction to 600 mg. It is also hard to time the drug because of the need to take it on an empty stomach (no food for 2 hours before and 2 hours after). It seems to me that the worst period is from 6 to 12 hours after I take it, so for now, I take the medication around 8 pm and have a snack at 10 pm. That seems to make me ok for most of the next day. I am wondering if anyone has any advice on when to take the medication and how to minimize the side effects.

October 9, 2014 at 4:24 pm  #1266406    
JimC Forum Moderator
JimC Forum Moderator

Hi cloeginger,

Welcome to GRACE. Glad to hear that ceritinib (Zykadia) has been effective for you, although I wish you weren’t having so much trouble with it.

Here are a couple of GRACE videos in which ceritinib and its side effects are discussed:

http://cancergrace.org/lung/2014/07/14/asco_2014_alk_positive_new_hope_zykadia/

http://cancergrace.org/lung/2014/04/03/alk-positive-lung-cancer-forum-2014-next-generation-alk-inhibitors/

I hope this helps.

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

October 10, 2014 at 7:27 am  #1266422    

Craig

I don’t have personal experience with it and so don’t have any specific suggestions you haven’t already thought of (e.g., eating some stomach-comforting food in 2 hours before & after). From my Xalkori experience, though, maybe it’s useful to stay upright for at least an hour after taking a dose. FWIW, as you know, gastrointestinal side effects are common with Zykadia (ceritinib). If it gets too bad, your oncologist might try reducing the dosage a little, but if it were me I’d try to grin and bear it if I could (or maybe I should say grimace and bear it?).

Best hopes,

Craig in PA


- Stage IV never-smoker ROS1-driven m-BAC indolent adenocarcinoma
– Dr. Alice Shaw’s Xalkori (crizotinib)-for-ROS1 trial @ MGH, Boston (5 yrs)
– Currently carboplatin + pemetrexed (Nov 2016+)

October 10, 2014 at 10:17 am  #1266428    

double trouble

To Aunt Tootsie (Lori)

I don’t know if you’re still logging in or checking GRACE any more. I see your picture is missing. But I do hope you’ll see this. Lori I just can’t imagine what you are going through. I am in shock and in pain, and I feel terrible that I didn’t see your post about your beloved son Chris sooner than this. I’ve been off Xalkori for a year now and just haven’t been checking the forums.

I want you to know that you are family here, and I hope you will continue to keep us informed of how you are doing. I understand that you have probably put your own needs last in lieu of the fact that Chris left a wife and three teenage children. I imagine you are trying to hold them together during this difficult time.

I just want to say please don’t neglect yourself. You’ve had such a great run on Xalkori, and you’ve been so supportive of the other patients and caregivers here, it would be a terrible loss if you were to decide not to return to GRACE. I know that your comments and encouragement helped get me through some very rough times.

Please know that I hold you in my heart and I ache for you, as I have a son the same age, and a granddaughter the same age, and if I lost my son right now I think I would lose myself. Please come back to us Lori. We miss you and we are so sorry for your loss.

Debra

October 10, 2014 at 2:50 pm  #1266429    

cloeginger

Thank your for your advice regarding ceritinib. I’ll try staying upright and let you know if it helps. I think Dr Shaw mentioned that there were additional food studies with ceritinib being carried out, and I was hoping that some of the eating restrictions might be loosened a little, but I haven’t seen anything more on that.
You are right though Craig, this medication has had a very good effect and if I have to I will just live with the side effects! Thanks again.

October 10, 2014 at 8:24 pm  #1266433    
Dr West
Dr West

Taking it at night in hopes of sleeping through nausea (at least relatively mild nausea) is one of the best tricks, which you’re already doing.

Otherwise, patients may require more than one dose reduction, and patients have done well with dosing down to 450 mg or even sometimes lower than that.

Good luck.

-Dr. West

October 11, 2014 at 12:13 pm  #1266444    

aunttootsie001

Well I’m at a loss as far as the picture will work on it! As far as my son Chris, you might have guess his body just couldn’t take the Radiation. Unfortunately after being on life Support for 3 days the Dr’s said his organs and brain waves were shutting down. The 17th was the worst Day of my life! As a mother, a mother who is hanging in there 3 years now the one thing I wasn’t expecting was for us to have to let him go! Taking him off life support and watching him slowly go was a nightmare. I was there and saw him go and I still can’t believe it! It is just devastating to look at pictures of him all I do is cry! Since July 17 I have gotten a little better but I still find it hard to except! My Daughterinlaw has ashes for me and I can’t wait to get them. I still haven’t seen any sign from him. I’m not sure what I’m looking for. I’m hoping once I have his ashes in my house I’ll see a sign. He was my oldest but as every mother knows they are always your baby! He has 3 teen boys who definitely needed him here! Thanks for you support guys! Debra I’m so happy your doing well! Lorrie!

October 12, 2014 at 10:39 am  #1266450    
catdander forum moderator
catdander forum moderator

Lorrie, I’m so glad to hear from you. I think of you often and worried when your picture disappeared. I can’t imagine your pain but want to let you know I include you in my meditations and send peace and strength to you. My dad also had 3 teen sons when he passed, and 2 daughters, I was 11. It was very difficult and I still miss him.
Sending much love, peace, and strength wrapped in hugs,
Janine


My husband, 8/09 53 @ dx stage III squam nsclc R. pancoast tumor
Destruction of 3 ribs, touching brachial plexus.
6/09-8/09 2 core and 1 VATS undx biopsies. Open thoracotomy for 1 positive biopsy (unresectable)
9/09 Chemo/rads curative intent
11/09 MRI by pancoast specialist surgeon spine met found undiagnosed Rad to spine, Chemo continued thru 6 cycles
Tarceva maintenance 2/10
11/10 3cm tumor L lung, undx core bx w/collapsed lung. Gemzar, 12/10 through 7/12
NED 3/12, stop tx 7/12. Remains NED as of 9/16
Unanswerable question. Was it ever metastatic?

October 13, 2014 at 11:43 am  #1266473    

cloeginger

Dear Dr. West and Craig, thank you both for your advice. I am continuing to take the drug in the evening and sitting up for a while after I take it, and the last two nights have been much better.

January 13, 2015 at 10:54 am  #1268039    

suejg

I’m shocked! A few minutes ago, the NP gave us Gary’s Foundation One results and then sent us in for his regularly scheduled taxotere infusion. Gary doesn’t seem to fit the ROS1 profile as a 63-year-old, Caucasian ex-smoker, but we’re surely not going to question the results!

I’m so excited and want to start a targeted treatment, but the onc isn’t ready to make a recommendation/change. Apparently, she is considering recommending a clinical trial. Seems like we should get rolling on xalkori, but we’re so new to the ROS1 club, that my head is spinning. I’m so hopeful that this will help improve Gary’s condition and response. He’s had a rough time this past month, and I don’t want him to slip any further. He is on his third line of treatment, and it doesn’t seem to be helping. The onc is sending him for a scan to verify.

I’m not sure if this is the appropriate place for this post, so please let me know if it is not. Also, if there is a specific site I should visit for ROS1 info, please let me know.

We would appreciate any insights. Thank you so much!


Husband age 63 with stage IV adenocarcinoma, dx in 10/2013 with metastatic pleural effusion. Repeated thoracenteses and then PleurX catheter used to drain large effusions. First line chemo with cetuximab, carbo, taxol and bevacizumab (clinical trial), second line with pemetrexed, and third line started 12/23/14 with taxotere. Developed messenteric metastasis and ascites requiring first paracentesis in 1/2015. Foundation One testing showed ROS1 alteration in 1/2015.

January 13, 2015 at 3:41 pm  #1268040    

aunttootsie001

Hi Janine! Thank You for your support! I am still struggling! This weather here in Ohio doesn’t help! It helps when I can get outside and walk!
Not to forget Suejg, I’m not sure what stage your hubby is in. If he is still curable then I can see them putting off the target drug. I think most the target drugs aren’t able to cure you. I am on Xalkori and it is holding my Cancer at bay. It hasn’t or ever will cure me or put me in Remmision. Don’t get me wrong if there is ever a drug that they think could cure me I’d be first in line! I am Stage 4. Lorrie

January 13, 2015 at 4:00 pm  #1268041    
catdander forum moderator
catdander forum moderator

A big congratulations on finding the ROS1 mutation. I’ll make this shorter because me darn router caused me to loose my last post to you. I see you’ve found the ALK ROS1 thread. Craig’s super, helpful, knowledgeable and will answer to that thread anytime.

Usually a scan is taken before a new treatment is started to get a baseline look. If you don’t have an appointment there is every reason to call the onc to ask about the thought process behind the trial and continued use of taxan. There may be a good reason. However it is appropriate to worry about the downhill motion of your husband’s health. You don’t want him to get too sick for any treatment and xalkori is the first choice (I’m a little behind on ROS1 and know trials are promising so I could be wrong).

Congrats again, Gary’s a lucky guy to have you!
Take care of yourself too,
Janine


My husband, 8/09 53 @ dx stage III squam nsclc R. pancoast tumor
Destruction of 3 ribs, touching brachial plexus.
6/09-8/09 2 core and 1 VATS undx biopsies. Open thoracotomy for 1 positive biopsy (unresectable)
9/09 Chemo/rads curative intent
11/09 MRI by pancoast specialist surgeon spine met found undiagnosed Rad to spine, Chemo continued thru 6 cycles
Tarceva maintenance 2/10
11/10 3cm tumor L lung, undx core bx w/collapsed lung. Gemzar, 12/10 through 7/12
NED 3/12, stop tx 7/12. Remains NED as of 9/16
Unanswerable question. Was it ever metastatic?

January 13, 2015 at 4:13 pm  #1268042    

suejg

Thanks, Lorrie. Gary has also been stage IV since his dx in 10/2013. It sounds like it may be standard to determine if a drug is working before switching to another. So, I guess we should wait a few weeks until we can get a new scan and can meet with the onc at the end of this month. It’s just so hard to see him struggle like he is now when it looks like there may be something that may work better for him. I worry that he is deteriorating and that waiting could harm him. Patience is apparently not my virtue.


Husband age 63 with stage IV adenocarcinoma, dx in 10/2013 with metastatic pleural effusion. Repeated thoracenteses and then PleurX catheter used to drain large effusions. First line chemo with cetuximab, carbo, taxol and bevacizumab (clinical trial), second line with pemetrexed, and third line started 12/23/14 with taxotere. Developed messenteric metastasis and ascites requiring first paracentesis in 1/2015. Foundation One testing showed ROS1 alteration in 1/2015.

January 13, 2015 at 4:19 pm  #1268043    

aunttootsie001

I only had 2 infusions of Chemo and White count went down and for 11 weeks wouldn’t come up! But I know how you feel while on the Chemo. So yes I can see why you’d like him off of it! Let us know when he switches and we’ll be happy to give tips! Lorrie

January 13, 2015 at 4:27 pm  #1268044    

suejg

Thank you so much, Janine! I’m doing my best to keep Gary going and hope he will improve rather than decline more during the next few weeks. It may be the chemo (and Neulasta) that’s beating him up and causing pain, nausea, and SOB. We’ll hang in there.


Husband age 63 with stage IV adenocarcinoma, dx in 10/2013 with metastatic pleural effusion. Repeated thoracenteses and then PleurX catheter used to drain large effusions. First line chemo with cetuximab, carbo, taxol and bevacizumab (clinical trial), second line with pemetrexed, and third line started 12/23/14 with taxotere. Developed messenteric metastasis and ascites requiring first paracentesis in 1/2015. Foundation One testing showed ROS1 alteration in 1/2015.

January 13, 2015 at 4:45 pm  #1268046    

Craig

Yes, Sue, this is one of the places you’ll find some other people interested in talking about ROS1 (and the more common yet somewhat similar ALK).

Yes, ROS1 is less common in older patients and in smokers (though 63 isn’t really as old as you’re imagining), but a portion of it is found among them. If I recall correctly, the early research was suggesting for example that roughly 10% of each ALK and ROS1 was found in smokers, and of course age alone isn’t any reason to discriminate if the testing cost isn’t more important than finding out if there’s a chance of something useful. I’d imagine that quitting smoking some time ago really helped.

Having a ROS1+ diagnosis doesn’t guarantee a great benefit, but the odds are good and probably beat another type of chemo.

I’d have guessed that Alimta (pemetrexed) + a platinum-based chemo would have been tried as one of his prior three kinds of treatments, was it, and did it help? Odds of that being helpful might favor a never or light smoking history though (not necessarily ALK or ROS1 patients more than others as some might hypothesize), so I can’t guess the odds of benefit to your man.

To join the original Xalkori (crizotinib) for ROS1 trial (the one I’m in) they will need baseline scans showing measurable cancer within something like 28 days of starting that trial. And it does make sense to want to know if the current chemo is helping or not even if you wanted to switch now so you’d know if it would be something worth finishing trying someday. BTW, when I joined the trial I also needed a abdomen/pelvis scan, so don’t be surprised if there are a couple of reasons to re-scan if you consider that trial rather than an off-label Rx if insurance wouldn’t decline paying.

Best hopes,

Craig in PA


- Stage IV never-smoker ROS1-driven m-BAC indolent adenocarcinoma
– Dr. Alice Shaw’s Xalkori (crizotinib)-for-ROS1 trial @ MGH, Boston (5 yrs)
– Currently carboplatin + pemetrexed (Nov 2016+)

January 13, 2015 at 5:34 pm  #1268049    

suejg

Hi Craig. Gary did have Alimta alone as his second line of treatment, but he had some small progression after three months, so the onc stopped tx. It looks like your trial is also at Karmanos in Detroit, so that may be a good option for us. How often do you have to travel to the trial center?


Husband age 63 with stage IV adenocarcinoma, dx in 10/2013 with metastatic pleural effusion. Repeated thoracenteses and then PleurX catheter used to drain large effusions. First line chemo with cetuximab, carbo, taxol and bevacizumab (clinical trial), second line with pemetrexed, and third line started 12/23/14 with taxotere. Developed messenteric metastasis and ascites requiring first paracentesis in 1/2015. Foundation One testing showed ROS1 alteration in 1/2015.

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