ROS 1 or other marker testings?/ EGFR 2nd/3rd/4th line treatments?

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This topic contains 9 replies, has 5 voices, and was last updated by  Dr West 2 years ago.

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June 28, 2012 at 3:35 pm  #12102    

lindizzima

Hi there,

I’m new to this, but very thankful there are forums like these around. My mom’s bio is in the signature. Currently, our onc has waited to treat Mom w/ anything new (right now, only moderate coughing), saying not to ‘poison’ her/make her more sick if she’s not too ‘sick/symptomatic’. Our original (retired) onc says ‘do something – the earlier the better’. Our concern: treating the ‘worst’ will be much harder than controlling/maintaining small progression. Seems some drs don’t track CEA, but hers is consistent w/ scans, cough, etc.& it’s through the roof right now.

From the last marker testing, ALK gene amplification or polysomy of chromosome 2 & EGFR Mutation exon 19 deletion (original biopsy tissue). Is this significant, useful?

She’s on year 8 & has had lots of treatments – are there others for those w/ EGFR resistance? Are there drugs on the horizon that she can try? BIBW-2992? We think she was on placebo during her clinical trial. Cetuximab/Erbitux? The onc is strongly considering Navelbine, but it sounds like it can be very harsh.

What’s a sulcus metastatic nodule? We read Dr. Weiss’ article about combining local radiation with other therapy. Is this an option to consider?

After 1+ yr Avastin/Zometa maintenance & ~1 yr of progression/mets, our onc now suggests us getting ROS1 marker testing. From reading, sounds like since she’s EGFR pos, she’s probably not ROS1 pos. Thoughts? He also said that we’d probably have to pursue the marker testing ourselves since ins doesn’t cover it. I’m at a loss: where to begin, how to proceed, where to go for it, it is even worth it? He wants to wait for these results before considering new treatment. We’ve heard about MGH (A. Shaw) & U Colorado (R. Camidge). (Mom is in FL/we’re in AZ) Any suggestions for drs or marker testing? Would another biopsy now be warranted to see if her tumors have changed? Would that help with the marker testing & in choosing a treatment?

Thanks for your support.


Mom (Cecilia), 72.5, Asian, Never Smoker, Dx 9/04 – NSCLC Adeno w/ BAC;; LOBECTOMY: Rt-mid (11/04);; ADJUVANT CHEMO: Gemzar/Paraplatin/Zofran (12/04-2/05) Stable, cough gone~ 1yr;; PET: growth/activity. (4/07-7/07); BIOPSY (07/07): Confirm BAC & Adeno, EGFR muta pos; TARCEVA (~14 mos 9/07–12/08), 3 mos into no PET activity/shrink/no change;; BIBW-2992 (AFATINIB) (~7 mos 12/08–6/09): Dbl-blind Clin Trial, CEA inc/cough worse/ bone mets;; ALIMTA (PEMETREXED) (10 mos 6/09–4/10) Cough improved/CEA down;; CT: New areas (missed in 9/09)/CEA inc (4/09).;; MARKER TEST: 1) EGFR pos, 2) ERCC1 low (5/10);; TARCEVA (2nd time): Bone activity inc/tumor growth/stronger cough (6/10–10/10);; CARBO/TAXOL 7 cyc. (12/10-3/11) No growth/shrink/no new areas/low PET activity;; AVASTIN/ZOMETA maintenance: (3/11–present);; 5/11 PET/CT: Negative Exam (no neoplasm);; 8/11, 11/11 PET/CT: inc lung/bone activity;; 2/12, 5/12 PET/CT: Old/new tumor/bone growth/activity;; MARKER TESTING (3/12) (orig lobect tissue). 1) ALK gene amplification or polysomy of chromosome 2, 2) EGFR deletion exon 19.

June 28, 2012 at 6:04 pm  #12106    

laya d.

Hi There – -

Let me be the first to welcome you to GRACE. I’m so sorry to read about your Mom’s disease. . .but an 8 year survivor is pretty impressive.

I AM NOT A DOCTOR AND HAVE NO MEDICAL TRAINING WHATSOEVER – - but, while waiting for the docs to come online to answer you directly, I recall that just in the past few days Dr. Weiss stated in a thread that EGFR activating mutations and ROS-1 are mutually exclusive. I see from your signature that your Mom’s EGFR Exon 19 activating mutation was recently reconfirmed (in March, I believe) – - but that the testing was done on her original biopsy tissue. I can tell you that my Mom recently has undergone a few biopsies at progression sites, and that all of them have shown the EGFR activating mutation, even the nodule that had morphed from adeno to squamous and/or those that show a TKI resistance mutation. So, my non-medially-trained hunch is that if your Mom is biopsied at her progression sites, the activating EGFR mutation will likely show up (unless a new primary cancer is discovered) – - but that the biopsies also will show resistance (like the T790m mutation, etc.) and no ROS-1. Again, just my guess here. . .

But, let’s see what the doctors have to say about all this. . .

Laya


1/10 – My Mom (58) dx w/ NSCLC-Adeno 3a; 1 cycle of neoadjuvent Carbo/Alimta before finding out EGFR+ (Ex. 19), then switched to 7 wks of neoadjuvent Tarceva/150 mg (major shrinkage); 4/10 – right pneumonectomy; 6/10 started 3 rounds of adjuvent Cis/Alimta w/ concurrent chest radiation (7 wks); 8/10 – NED; 11/10 – small nodule in left lung; 1/11 – 3 small nodules in left lung, start Tarceva/100 mg; 4/11 – suspected sclerotic met to hip, continue w/ Tarceva, add XGEVA, brain MRI clear; 9/11 – solitary 3 cm met (adeno w/ T790m mutation) to cerebellum, surgery and gamma knife, up Tarceva to 150 mg; 11/11 – 2 left lung nodules growing, biopsy on 1 shows mutation from adeno to squamous (shocker!), brain MRI clear, continue Tarceva & Xgeva; 2/12 – brain MRI clear, CT scan, remaining nodule slightly bigger – – monitor for now, Tarceva (reduced to 100 mg) & Xgeva continued; 4/12 progression and rebiopsy (confirmed adeno), stop Tarceva, switch to Carbo/Alimta; 6/12 maintenanceAlimta; 8/12 back to Tarceva; 10/12 Gemzar; 11/16 difficulty breathing; 12/12 hospice initiated…my Mom passed away peacefully on 12/19/12. Heartbroken.

June 28, 2012 at 9:42 pm  #12125    

Dr West

I don’t understand the result given for ALK — it should be a clearer “YES, there’s an ALK rearrangement by defined criteria”, or “No”. But as Laya noted, both ALK rearrangements and ROS-1 rearrangements are extremely uncommon if not completely mutually exclusive with an EGFR mutation. ROS-1 testing is really only available at MGH or University of Colorado, and one of the people there might also be among the best qualified to consider whether there is a feasible option for “acquired resistance” after an EGFR mutation.

Otherwise, I would suggest that you search the site for “acquired resistance” to learn more about how we’re thinking about options in this setting, though the short answer is that there is nothing standard and that we’re still struggling with clinical trials to help us identify potentially promising avenues for the future.

-Dr. West

PS: A little TOO much detail in the signature. We’re trying to help a lot of people in limited time, so I’ll make a plea for BREVITY and well defined, limited questions (and not many at once).


Howard (Jack) West, MD
Medical Oncologist

Views expressed here represent my opinion, not those of GRACE or Swedish Cancer Institute. This information does not constitute medical advice and is intended to supplement and not replace medical information provided by your doctor.

June 28, 2012 at 10:16 pm  #12131    

Jazz

Hello,
As Laya mentioned, did your Mom test positive for a T790 mutation (which occurs in about 50% of mutants after TKI treatment)? If so, she might qualify for a trial of an agent against this mutation, CO-1686, which is at U of CO, UCLA, and a center in Michigan. It’s currently at Phase I dose escalation, but there is already a waiting list at Colorado. Alternatively, also at CO is a trial of Afatinib (BIBW2992) + Cetuximab, although she may be disqualified as it appears she’s already had that agent. If the study was unblinded, you can confirm whether she indeed received it or placebo.

Best of luck and yes, please shorten signature :)

Jazz


Non-smoker, Dx 6/06 Stage IV Adeno. EGFR+ (exon 19 del), T790m+. Trial: 2cyc Carbo/Doce/Avastin + 2 w/Gem 8 – 12/06; Avastin maint. 1 – 4/07. Alimta + Tarceva 5/07 – 2/09. NED to 8/09. Tarceva 150 9/09-5/11, SBRT/XRS to lung & spine met 2/11. Trial MK2206 (AKT inhibitor) + Tarceva 5 – 12/11. Afatinib+cetuximab trial 2/12 -2/13. LL collapsed. 1/13 PET – new bone & adrenal mets. 4 cyc Carbo-Gem-Tarceva 5/13. Brain MRI 10/13 – clear. Lost Dad to LC 5/13.Anti-PDL1@Angeles Clinic?

June 28, 2012 at 10:17 pm  #12132    

Jazz

I meant to add that your Mom sounds tough and I admire her 8 years!! Good for her and your family!

Jazz


Non-smoker, Dx 6/06 Stage IV Adeno. EGFR+ (exon 19 del), T790m+. Trial: 2cyc Carbo/Doce/Avastin + 2 w/Gem 8 – 12/06; Avastin maint. 1 – 4/07. Alimta + Tarceva 5/07 – 2/09. NED to 8/09. Tarceva 150 9/09-5/11, SBRT/XRS to lung & spine met 2/11. Trial MK2206 (AKT inhibitor) + Tarceva 5 – 12/11. Afatinib+cetuximab trial 2/12 -2/13. LL collapsed. 1/13 PET – new bone & adrenal mets. 4 cyc Carbo-Gem-Tarceva 5/13. Brain MRI 10/13 – clear. Lost Dad to LC 5/13.Anti-PDL1@Angeles Clinic?

June 29, 2012 at 10:28 am  #12158    

lindizzima

Thank you so much for your responses and warm welcomes.

Laya, that’s what I thought about the ROS1 and EGFR being mutually exclusive. And that’s why it was confusing as to why our onc suggested the test in the first place. I guess we’ll ask about being rebiopsied again, but the onc didn’t really want to go there because of her age and such. Thanks for sharing the results of your mom’s rebiopsies.

Dr. West, the report stated that there was 35% of cells indicating the ALK, but the cut off is 40%. So there wasn’t enough to actually say that it was ALK positive. So I was just wondering if others have seen that too. Another little flag in my mind. Do you happen to know whether the general public can reach out to the dr’s at MGH or U Col to see if more testing can be done? Or does it have to go through another physician? We’ve always had our onc contact the labs or test sites and now he’s saying that it’s up to us, so I wasn’t sure how to go about doing that.

Jazz, in the last marker testing, the T790 didn’t show up. Only the exon 19. We’re not sure if this is due to the fact that it was done on her original tissue (which didn’t get any treatment). I guess asking about a current rebiopsy would be good, right? Thanks for the additional info of different trials going on!

ps. thanks for the feedback on the sig. I hope it’s better! I tried my best ;) If you think I should shorten it more, feel free to let me know. thx!

And we are very thankful for mom’s 8 years of survival! Thanks for the encouragement!


Mom (Cecilia), 72.5, Asian, Never Smoker, Dx 9/04 – NSCLC Adeno w/ BAC;; LOBECTOMY: Rt-mid (11/04);; ADJUVANT CHEMO: Gemzar/Paraplatin/Zofran (12/04-2/05) Stable, cough gone~ 1yr;; PET: growth/activity. (4/07-7/07); BIOPSY (07/07): Confirm BAC & Adeno, EGFR muta pos; TARCEVA (~14 mos 9/07–12/08), 3 mos into no PET activity/shrink/no change;; BIBW-2992 (AFATINIB) (~7 mos 12/08–6/09): Dbl-blind Clin Trial, CEA inc/cough worse/ bone mets;; ALIMTA (PEMETREXED) (10 mos 6/09–4/10) Cough improved/CEA down;; CT: New areas (missed in 9/09)/CEA inc (4/09).;; MARKER TEST: 1) EGFR pos, 2) ERCC1 low (5/10);; TARCEVA (2nd time): Bone activity inc/tumor growth/stronger cough (6/10–10/10);; CARBO/TAXOL 7 cyc. (12/10-3/11) No growth/shrink/no new areas/low PET activity;; AVASTIN/ZOMETA maintenance: (3/11–present);; 5/11 PET/CT: Negative Exam (no neoplasm);; 8/11, 11/11 PET/CT: inc lung/bone activity;; 2/12, 5/12 PET/CT: Old/new tumor/bone growth/activity;; MARKER TESTING (3/12) (orig lobect tissue). 1) ALK gene amplification or polysomy of chromosome 2, 2) EGFR deletion exon 19.

  • This reply was modified 2 years ago by  lindizzima.
June 29, 2012 at 1:23 pm  #12161    

catdander forum moderator

Welcome lindizzima, I too am NOT a medical professional but have a couple of comments to add. Your signature is still quite long but then your putting 8 years worth of treatment history into it. Congratulations.

T790 is most usually or maybe exclusively (I’m not sure) found in tki, such as tarceva treated patients who have become resistant to the drug. So a biopsy from a tumor from progression on tarceva would need to be taken.
Please someone let me know if I’ve misspoken.

You may call directly to the offices of the doctors from which you want opinions.

Also Dr West suggested using our search to find information about tarceva resistance. Let us know if you have any difficulty.

Janine


My husband, 53 @ dx of stage 3 squam nsclc R. pancoast tumor 8/09 caused destruction of 3 ribs, touching brachial plexus. 2 core and 1 VATS undx biopsies. Open thoracotomy for 1 positive biopsy (unresectable). Chemorads, 9/09. MRI by pancoast specialty surgeon 11/09 spine met found, stage IV, Rad to spine, Chemo changed from cis/etop to navelbine/carbo. 6 cycles total. Tarceva 2/10-11/10. 3cm tumor L lung, biopsy undx w/collapsed lung. Gemzar, 12/10 through 7/12. NED 3/12, stop tx 7/12. Remains NED as of 2/14.

June 29, 2012 at 6:39 pm  #12179    

Dr West

lindizzima,

Yes, the signature now is a much better balance. I realize that your signature will be long pretty much no matter what, as a byproduct of your mother’s 8 year history — a very good problem to have.

That cutoff, which is somewhat arbitrary, is a predicament. I’ve spoken with the folks leading the development of XALKORI, and they recognize the challenge of having developed a test that measures a continuous variable (there are gradations, not just a yes/no answer) wth a cutoff: I think the best answer is that we don’t know how effective or ineffective XALKORI is/would be in people who fall a little below the cutoff.

I am pretty sure you don’t need to have a physician shepherd you through the process of being tested at Mass General or University of Colorado. The problem is that I think that there isn’t any standard practice of testing people who aren’t patients there for a whole battery of tests. The question of how patients from all over can get investigational testing done at one of a very small number of labs is a moving target, but I think the overall trend will be toward increasing access. However, that doesn’t mean these tests will be standardly covered by insurers. Instead, such testing may well become more readily available, but potentially largely paid out of pocket.

I’ll be announcing our webinar topics for the next few months, and our August guest will be Dr. Dara Aisner, a molecular pathologist at the University of Colorado who is actually running all of these tests and can provide a very helpful perspective here.

-Dr. West


Howard (Jack) West, MD
Medical Oncologist

Views expressed here represent my opinion, not those of GRACE or Swedish Cancer Institute. This information does not constitute medical advice and is intended to supplement and not replace medical information provided by your doctor.

July 2, 2012 at 3:33 pm  #12326    

lindizzima

Thanks, Janine. I will definitely search around some more (per Dr. West’s suggestion) and read up on the tarceva resistance. And for sure will let you guys know if I need some help with it!

Dr. West, thanks for sharing your insight on XALKORI and the testing. I’m not sure if you know, but do you happen to know what the range of the costs could/may be for getting tests run our of pocket? I’ll def be contacting them and asking them directly, but just thought I’d see if you happen to know.

I will definitely be looking out for your August webinar!

Linda.


Mom (Cecilia), 72.5, Asian, Never Smoker, Dx 9/04 – NSCLC Adeno w/ BAC;; LOBECTOMY: Rt-mid (11/04);; ADJUVANT CHEMO: Gemzar/Paraplatin/Zofran (12/04-2/05) Stable, cough gone~ 1yr;; PET: growth/activity. (4/07-7/07); BIOPSY (07/07): Confirm BAC & Adeno, EGFR muta pos; TARCEVA (~14 mos 9/07–12/08), 3 mos into no PET activity/shrink/no change;; BIBW-2992 (AFATINIB) (~7 mos 12/08–6/09): Dbl-blind Clin Trial, CEA inc/cough worse/ bone mets;; ALIMTA (PEMETREXED) (10 mos 6/09–4/10) Cough improved/CEA down;; CT: New areas (missed in 9/09)/CEA inc (4/09).;; MARKER TEST: 1) EGFR pos, 2) ERCC1 low (5/10);; TARCEVA (2nd time): Bone activity inc/tumor growth/stronger cough (6/10–10/10);; CARBO/TAXOL 7 cyc. (12/10-3/11) No growth/shrink/no new areas/low PET activity;; AVASTIN/ZOMETA maintenance: (3/11–present);; 5/11 PET/CT: Negative Exam (no neoplasm);; 8/11, 11/11 PET/CT: inc lung/bone activity;; 2/12, 5/12 PET/CT: Old/new tumor/bone growth/activity;; MARKER TESTING (3/12) (orig lobect tissue). 1) ALK gene amplification or polysomy of chromosome 2, 2) EGFR deletion exon 19.

July 2, 2012 at 5:35 pm  #12336    

Dr West

Sorry — I’ve heard numbers in the $1500-1800 range, but I don’t know if that’s accurate right now. There are more labs offering ALK and other molecular testing all the time, so my hope is that this will lead to a more competitive marketplace and prices coming down.

-Dr. West


Howard (Jack) West, MD
Medical Oncologist

Views expressed here represent my opinion, not those of GRACE or Swedish Cancer Institute. This information does not constitute medical advice and is intended to supplement and not replace medical information provided by your doctor.

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