immunotherapy and EGFR

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February 7, 2017 at 8:19 am  #1290015    

kkh130

Hello,

I would like to know if any doctors here are using combination of immunotherapy and TKI drug for EGFR+ patients. How about combination of two immunotherapy drugs or combination of immunotherapy and chemo? ***Will these combination therapy increase the response rate for EGFR+ patients?***

My dad’s most recent ct scans showed progression on TAGRISSO. He was diagnosed of leptomeningeal metastasis Nov 2015. His brain MRI (Dec 2016) still shows stable. I don’t feel comfortable for him to be on immunotherapy alone because I’ve heard the response rate is just 5-10% for EGFR+ patients and most of them ended up in severe health conditions that require hospitalization.

Kkh


Diagnosed in 2014 stage 4 nsclc. EGFR+ (also positive for t790m). 1 year on Tarceva, then 8 months on Rociletinib, then WBR following by 7 months on Tarcrva pulse/carboplatin/avastin/alimta, then 7 month on Tagrisso. Was diagnosed leptomeningeal metastasis Nov 2015. Now has 10cm big tumor and multiple nodules with different sizes. Most recent guardant test (Feb 2017): TP53 C277F 29.8  EGFR Exon 19 Deletion 20.1  EGFR AMP ++  MET H1112Y 0.1  MET AMP +  FGFR1 AMP ++  PIK3CA AMP +  CCNE1 AMP ++  BRAF AMP +  MYC AMP ++  Additional Alterations  BRCA1 R7C 0.3  MTOR K1197E 0.2  NF1 V1762V 0.2  MET E436K 0.1  JAK2 V617F ND  MAP2K2 E66K ND 

February 7, 2017 at 9:17 am  #1290016    

kkh130

If immunotherapy is no better than chemo for him, what chemo drugs are best for him (any chemo drugs can crosss blood brain barrier?). He used carboplatin/alimta/avastin along with tarceva pulse before starting tagrisso.

Kkh


Diagnosed in 2014 stage 4 nsclc. EGFR+ (also positive for t790m). 1 year on Tarceva, then 8 months on Rociletinib, then WBR following by 7 months on Tarcrva pulse/carboplatin/avastin/alimta, then 7 month on Tagrisso. Was diagnosed leptomeningeal metastasis Nov 2015. Now has 10cm big tumor and multiple nodules with different sizes. Most recent guardant test (Feb 2017): TP53 C277F 29.8  EGFR Exon 19 Deletion 20.1  EGFR AMP ++  MET H1112Y 0.1  MET AMP +  FGFR1 AMP ++  PIK3CA AMP +  CCNE1 AMP ++  BRAF AMP +  MYC AMP ++  Additional Alterations  BRCA1 R7C 0.3  MTOR K1197E 0.2  NF1 V1762V 0.2  MET E436K 0.1  JAK2 V617F ND  MAP2K2 E66K ND 

February 7, 2017 at 10:01 am  #1290017    
catdander forum moderator
catdander forum moderator

Hi K, I’m sorry to know your dad’s shown progression on tagrisso. I’d like to warn you if you’re not already familiar with the phenomenon; often a tki will allow some progression but only a little. Most nsclc specialists keep their patients on the tki if the progression is only in spot or 3 believing it keeps most of the cancer at bay until the progression is significant.

To your question, there are many trials testing the potential of immunotherapies combined with other therapies. What we know so far is that those with a driving mutation such as egfr don’t do very well at all on immunotherapies alone and chemo is still the first choice after tkis. There are many companies looking/doing trials for answers on how best use immunotherapies. Unfortunately the side effects profile seems to magnify when combined. The good thing about trials is that those conducting them give exceptionally good care to their patients. For now it’s the safest way to give combo immuno drugs and probably the only way because insurance isn’t likely to pay.

The most up to date info is a few months old but current. Dr. Weiss and to collegues discuss the possibilities of these types of trials in the 2nd link. Even though the topic is head and neck the info can to translated to nsclc as well.

http://cancergrace.org/lung/tag/immunotherapy-combinations/

http://cancergrace.org/hnscc/2016/08/02/asco-2016-treating-head-and-neck-cancer-using-immunotherapy-as-first-line-treatment-and-in-combinations/

http://cancergrace.org/lung/2015/12/08/gcvl_lu_immunotherapy_combinations_future_treating_lung_cancer/

I hope some of this is helpful and I hope your dad finds himself stable soon.
All best,
Janine

February 7, 2017 at 10:30 am  #1290018    
catdander forum moderator
catdander forum moderator

Dr. West commented on a blog post, “I don’t know of anything in particular — you or her doctor may be able to find something searching on clinicaltrials.gov. I must confess, however, that I would consider it far more likely that chemotherapy will be beneficial than to try a clinical trial as the first treatment after Tarceva in a patient with T790M-negative acquired resistance. It isn’t to say that I think a trial would be a bad idea, but I would be less inclined to favor a trial, with the benefits not established and totally unknown, compared to platinum doublet chemotherapy that has a known and well-established survival benefit, than as a later line where there isn’t a competing standard treatment with a well-established benefit.” It’s the very last post in the comments section. http://cancergrace.org/lung/2016/05/16/t790m-osi-vs-roci/#comment-10681

Carboplatin with paclitaxal is the most studied effective first line doublet. However many maybe most use alimta instead of pac for adeno because it’s felt that alimta has fewer side effects and maybe even more efficacy for those with a driver mutation though neither of these traits have been properly vetted, as long as alimta is offered at some point.

Janine

February 15, 2017 at 8:35 am  #1290077    

kkh130

Hi Janine,

Thank you for responding to my questions. Do you know any doctors try the combination of afatinib and cetuximab on their patients after tagrisso no working? Any TKI will work after tagrisso?

Kkh


Diagnosed in 2014 stage 4 nsclc. EGFR+ (also positive for t790m). 1 year on Tarceva, then 8 months on Rociletinib, then WBR following by 7 months on Tarcrva pulse/carboplatin/avastin/alimta, then 7 month on Tagrisso. Was diagnosed leptomeningeal metastasis Nov 2015. Now has 10cm big tumor and multiple nodules with different sizes. Most recent guardant test (Feb 2017): TP53 C277F 29.8  EGFR Exon 19 Deletion 20.1  EGFR AMP ++  MET H1112Y 0.1  MET AMP +  FGFR1 AMP ++  PIK3CA AMP +  CCNE1 AMP ++  BRAF AMP +  MYC AMP ++  Additional Alterations  BRCA1 R7C 0.3  MTOR K1197E 0.2  NF1 V1762V 0.2  MET E436K 0.1  JAK2 V617F ND  MAP2K2 E66K ND 

February 16, 2017 at 5:19 am  #1290086    
JimC Forum Moderator
JimC Forum Moderator

Hi kkh,

There is some laboratory evidence that cetuximab may be effective in some cases of resistance to Tagrisso, but that hasn’t been proven in clinical trials:

”Most interestingly, in the presence of del 19 or L858R and T790M, C797S mutation leads to resistance to all current EGFR inhibitors (gefitinib, afatinib, WZ4002, CO-1686, and AZD9291), but L858R/T790M/C797S mutant remains partially sensitive to cetuximab. It remains to be determined whether cetuximab or cetuximab-based combinations are effective clinically in NSCLC patients that develop the L858R/T790M/C797S mutant clone.”http://jhoonline.biomedcentral.com/articles/10.1186/s13045-016-0290-1

So it’s an option that could be tried, especially if a new biopsy reveals the type of markers noted above.

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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