Crizotinib/ceritinib for ROS1 rearrangement intron 32 and tumor mutation burden

Portal Forums Lung/Thoracic Cancer ALK Inhibitors Crizotinib/ceritinib for ROS1 rearrangement intron 32 and tumor mutation burden

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June 8, 2017 at 10:39 pm  #1290841    

bh

Thanks to this forum, took mom to a university hospital for gene testing and the results were given to us today. The results read ROS1 rearrangement intron 32 and under additional findings, it says tumor mutation burden TMB-Low; 3Muts/mb. The therapies identified are Ceritinib and Crizotinib. How are these therapies different from one another? No therapies were identified for the tumor mutation.

Also did not understand how the ROS1 was identified when the body of the report says it is unclear if oncogenic rearrangement is present. It does say an activating ROS1 rearrangement is present (fusion).

I read an old article written by Dr. West which said that patients with the ROS1 rearrangement respond favorably to Alimta as well and patients with ROS1 who respond to Alimta have waited to try Crizotinib as a later resort. Mom’s test report also states that patients with ROS1 rearrangement have exhibited longer progression free survival on Alimta.

As mom is still responding to Alimta, no pleural effusion in 5 weeks, no breathlessness, appetite has returned, should these results just be treated as important information and no changes in treatment be considered at this point? Her onc did not order this testing and we hope to discuss the results with the onc at mom’s next visit.

13 other variants were also identified but none of them hold significance as not much is known about them in scientific literature at this time is what the report said. One of the variants was ROS L567V.

If you could point me to articles or information about ROS1 as is pertinent to these results or if you could share any input, I would be grateful.

Thank you so much.
Bee


77 yr old mom, never smoker, ER on 9/1/11 for breathlessness, diagnosed with malignant pleural effusion 9/8/11, stage 1V bronchiogenic adenocarcinoma of the lung. Tarceva 9/24/11; 4th thoracentesis on 9/26; diarrhea & nausea on 10/5 with rashes EGFR & ALK tests negative 10/7, stop tarceva 10/8, ER – 10/13, 5th thoracentesis, renal failure 10/15 – blood transfusion 10/27; Alimta, well tolerated; 11/9 stroke – lost right side and speech, 4/3 – hospitalized sugars of 803 due to decadron, 4/7 seventh round of Alimta with ongoing rehab for stroke. CT of 6/24/13 showed recurrence, re-start Alimta 7/11/13.On and off Alimta since 2013, usually NED and off chemo for periods of no less than 8 months to 14 months. Recent re-occurrence- Jan 2016, Alimta from Jan thru April 2016, NED April 2016. Re-occurrence of cancer Jan 2017, re-started Alimta. Tested positive for ROS1 June 2017, appt with onc to discuss future tx plans.

June 9, 2017 at 12:08 am  #1290843    
catdander forum moderator
catdander forum moderator

Here are the results from a quick Grace search. The first video on the list is the latest one with the most up to date thought. It suggests crizotinib to be the leading choice but in your mom’s case since she is already taking alimta and doing so well her onc will probably want to keep her on that for as long as it’s working and side effects are limited (not for nothing taking a daily pill may ease a lot of side effects brought on by weekly trips to the cancer center for IV infusions)

http://cancergrace.org/lung/tag/ros-1/

This is a long thread, 26 pages in the patient groups forum http://cancergrace.org/topic/alk-or-ros1-nsclc-patient-group

June 14, 2017 at 6:38 pm  #1290864    

bh

Dear Janine,
Thank you so very much for all the links and for the so prompt response. We have had out of town visitors to see mom, so sorry, I didn’t acknowledge your reply earlier. Have been going through the links over and over and hope to discuss the results with mom’s onc next week, mom has a chemo appointment.
I will keep you updated.
Thank you so much.
Bee


77 yr old mom, never smoker, ER on 9/1/11 for breathlessness, diagnosed with malignant pleural effusion 9/8/11, stage 1V bronchiogenic adenocarcinoma of the lung. Tarceva 9/24/11; 4th thoracentesis on 9/26; diarrhea & nausea on 10/5 with rashes EGFR & ALK tests negative 10/7, stop tarceva 10/8, ER – 10/13, 5th thoracentesis, renal failure 10/15 – blood transfusion 10/27; Alimta, well tolerated; 11/9 stroke – lost right side and speech, 4/3 – hospitalized sugars of 803 due to decadron, 4/7 seventh round of Alimta with ongoing rehab for stroke. CT of 6/24/13 showed recurrence, re-start Alimta 7/11/13.On and off Alimta since 2013, usually NED and off chemo for periods of no less than 8 months to 14 months. Recent re-occurrence- Jan 2016, Alimta from Jan thru April 2016, NED April 2016. Re-occurrence of cancer Jan 2017, re-started Alimta. Tested positive for ROS1 June 2017, appt with onc to discuss future tx plans.

June 20, 2017 at 2:08 pm  #1290882    

bh

Just a quick update.

Mom had both an onc appointment and an infusion appointment. The onc recommended mom stay on the Alimta as she has been responding to Alimta well since diagnosis. The onc feels we should keep the ROS1 mutation news in the back pocket if in the future mom stops responding to Alimta, I kind of agree with the onc. Why fix something if it ain’t broken?

Mom is on her 5th round of Alimta this session and is back to being her perky self.

Any reason (that I am overlooking) why we should consider Crizotinib over Alimta? I also read that Crizotinib has a tendency to not prevent brain mets. Mom has had no mets whatsover, knock on wood, with Alimta. That is another reason I am comfortable with the onc’s recommendation.

Thanks.
Bee


77 yr old mom, never smoker, ER on 9/1/11 for breathlessness, diagnosed with malignant pleural effusion 9/8/11, stage 1V bronchiogenic adenocarcinoma of the lung. Tarceva 9/24/11; 4th thoracentesis on 9/26; diarrhea & nausea on 10/5 with rashes EGFR & ALK tests negative 10/7, stop tarceva 10/8, ER – 10/13, 5th thoracentesis, renal failure 10/15 – blood transfusion 10/27; Alimta, well tolerated; 11/9 stroke – lost right side and speech, 4/3 – hospitalized sugars of 803 due to decadron, 4/7 seventh round of Alimta with ongoing rehab for stroke. CT of 6/24/13 showed recurrence, re-start Alimta 7/11/13.On and off Alimta since 2013, usually NED and off chemo for periods of no less than 8 months to 14 months. Recent re-occurrence- Jan 2016, Alimta from Jan thru April 2016, NED April 2016. Re-occurrence of cancer Jan 2017, re-started Alimta. Tested positive for ROS1 June 2017, appt with onc to discuss future tx plans.

June 20, 2017 at 3:08 pm  #1290883    
JimC Forum Moderator
JimC Forum Moderator

Hi Bee,

I’m glad to hear that your mom is feeling perky again and doing well on Alimta. I think her oncologist’s advice is pretty sound; as you say, it’s tough to justify switching treatments when the current regimen is working well.

As far as crizotinib and brain mets, in a podcast Dr. Camidge highlighted a possible difference between patients with ALK and ROS-1 rearrangements:

“Maybe the frequency of progression within the brain, which we know is somewhat of an Achilles heel for crizotinib and ALK-positive lung cancer — maybe that’s not such an issue with the ROS-1 rearranged patients simply because they have a lower frequency of deposits in the brain.”http://cancergrace.org/lung/2016/04/10/gcvl_lu_ros-1_rearrangements_defined/

Keep posting these positive updates…we love to hear them!

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

July 11, 2017 at 1:13 pm  #1291045    

bh

Hi Jim!

Hope you are doing well. Back again to report that mom’s CT looks good. Still researching Xalkori and all the links Janine and you pointed me to check out. I also stumbled upon some reference to Alimta being somewhat more effective in preventing/reversing brain mets. Mom has no mets but why not stick with the one that possibly prevents them. So more confused but sticking with Alimta for now.

Thanks so much for all your support and the time you give so unselfishly.
Best,
Bee


77 yr old mom, never smoker, ER on 9/1/11 for breathlessness, diagnosed with malignant pleural effusion 9/8/11, stage 1V bronchiogenic adenocarcinoma of the lung. Tarceva 9/24/11; 4th thoracentesis on 9/26; diarrhea & nausea on 10/5 with rashes EGFR & ALK tests negative 10/7, stop tarceva 10/8, ER – 10/13, 5th thoracentesis, renal failure 10/15 – blood transfusion 10/27; Alimta, well tolerated; 11/9 stroke – lost right side and speech, 4/3 – hospitalized sugars of 803 due to decadron, 4/7 seventh round of Alimta with ongoing rehab for stroke. CT of 6/24/13 showed recurrence, re-start Alimta 7/11/13.On and off Alimta since 2013, usually NED and off chemo for periods of no less than 8 months to 14 months. Recent re-occurrence- Jan 2016, Alimta from Jan thru April 2016, NED April 2016. Re-occurrence of cancer Jan 2017, re-started Alimta. Tested positive for ROS1 June 2017, appt with onc to discuss future tx plans.

July 11, 2017 at 1:23 pm  #1291046    

bh

Sorry, forgot to attach the links on Alimta and brain mets.

http://cancergrace.org/lung/2009/09/21/alimta-for-brain-mets/

http://cancergrace.org/lung/2007/10/24/chemo-for-brain-mets/


77 yr old mom, never smoker, ER on 9/1/11 for breathlessness, diagnosed with malignant pleural effusion 9/8/11, stage 1V bronchiogenic adenocarcinoma of the lung. Tarceva 9/24/11; 4th thoracentesis on 9/26; diarrhea & nausea on 10/5 with rashes EGFR & ALK tests negative 10/7, stop tarceva 10/8, ER – 10/13, 5th thoracentesis, renal failure 10/15 – blood transfusion 10/27; Alimta, well tolerated; 11/9 stroke – lost right side and speech, 4/3 – hospitalized sugars of 803 due to decadron, 4/7 seventh round of Alimta with ongoing rehab for stroke. CT of 6/24/13 showed recurrence, re-start Alimta 7/11/13.On and off Alimta since 2013, usually NED and off chemo for periods of no less than 8 months to 14 months. Recent re-occurrence- Jan 2016, Alimta from Jan thru April 2016, NED April 2016. Re-occurrence of cancer Jan 2017, re-started Alimta. Tested positive for ROS1 June 2017, appt with onc to discuss future tx plans.

July 11, 2017 at 5:19 pm  #1291047    
JimC Forum Moderator
JimC Forum Moderator

Hi Bee,

Thanks for the update and the good news on the scan. It’s hard to say just how effective Alimta is with regard to preventing or treating brain mets, but it seems to have worked well otherwise for your mom, so as you say it would be a tough choice to change treatment course until there is clear evidence that Alimta is no longer effective. It’s also possible that if disease is seen in the brain, it could be locally treated and Alimta resumed, assuming it is still effective elsewhere.

It’s good that you’re researching other options, but I agree that staying the course at this point makes a lot of sense. Keep those good updates coming!

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

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