Tagrisso resistance via C797S mutation - 1288526

Tue, 09/06/2016 - 10:13


If your patient develops resistance to Tagrisso via the C797S mutation , what is your current go to therapy?


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Hi Kempton,

I'm very sorry but there aren't any clinical trials (posted on clinicaltrials.gov ) yet that test hopeful 4 gen drugs.
There is some non clinical evidence that cetuximab is partially effective but again non clinical evidence means very little in the real world, but <span style="text-decoration:underline;">if it's an option</span> anyway I why not try it.
" 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

Other than EGFR tki treatments other standard stage IV nsclc treatments are available. http://cancergrace.org/lung/2010/10/04/lung-cancer-faq-2nd-line-nsclc-o…
Other options are to test for PD-L1 for possible immunotherapy options.

Keep hopeful,


Thank you Janine,

in the absence of possible 4th generation TKI's , are there any studies going on that are taking in patients that have become resistant to all TKI's ( combinations of traditional chemo , TKI's in combination with anti angiogenic drugs ?

I thought there is a study going on, matching patients depending on their mutations to chemo agents even if they have not been approved for a particular cancer site ?

Many patients must have become resistant by now after having taken Tagrisso over the last few years.
How are they being treated, and what are the preliminary results?

I have not become resistant yet, I hope. I will find out at the end of September ( 5 1/2 months after start of treatment )
But I'm studying the possible mutations that can occur and was wondering what you guys have chosen for your patients that are totally TKI resistant ?



Hi Kempten,

There's a great deal of focus on targeted therapies, which has lead to a dismissive attitude about chemotherapy among mutation-positive patients. Although we always hope for a very long-lasting response from targeted therapy, resistance often occurs, even beyond the third generation EGFR TKIs. But as Janine stated, standard chemotherapy remains a good option frequently chosen, and one that tends to be quite effective among EGFR mutation-positive patients. This issue was discussed by Dr. Greg Riely here.

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Thank you Jim,
I hope to get a few more months out of Tagrisso.




Hi Janine,
Thank you for sending the link above.
I had come across the EA1045 compound in combination with cetuximab during my research.
I think Dr Johnson at Dana Farber amongst others is involved in these experiments in mouse models ?
I actually saw him twice for a second opinion throughout my journey.
I will go back to him once the Tagrisso stops working.
Thanks again