immunotherapy and EGFR - 1290015

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-nec…
http://cancergrace.org/lung/2015/12/08/gcvl_lu_immunotherapy_combinatio…

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

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

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
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