Hi, I was diagnosed with Stage IV Lung Cancer last July due to EGFR egfr e746_a750del (19 del) mutation. I had 6 cm tumor in my left lung with mets to the right lung, ribs, brain, and pleural effusion. I am 42 yrs old, Asian, non smoker. I started Tarceva last August, and the primary tumor in my left lung shrunk by 50%, nodules in my right lung and brain disappeared, and pleural effusion was gone by Sep. But this didn't last long, as my tumor is back to the original size and there are new nodules in my lungs according to the CT scan I had yesterday (17 Feb). After 6 months on Tarceva, my Oncologist concluded that the drug is no longer working, and he ordered a blood test to check if I am 790M-positive. If tested positive, he would put me on Tagrisso.
My question: anyone has any ideas what could be potential treatments for 790M-negative patients? I learned there are alternatives such as afatinib and cetuximab, or chemo, and Rociletinib, but studies on this remain limited and current research indicate effectiveness of those drugs for 790M- negative treatments is relatively low.
Thanks.
Reply # - February 19, 2016, 08:04 AM
Hi Sunday,
Hi Sunday,
Welcome to Grace. I'm very sorry your cancer has progressed on tarceva but hope you have a chance to try tagrisso. I'll ask an oncologist to comment on your questions. Let us know how the blood test turns out.
All best,
Janine
Reply # - February 19, 2016, 08:32 AM
Hi Sunday, I am sorry to hear
Hi Sunday, I am sorry to hear the Tarceva seems to have stopped working but thank you for sharing your story.
I agree that testing for T790M makes the most sense, and Tagrisso is a very reasonable option if positive since this is effective in most patients whose tumors have the T790M mutation.
If the biopsy does not show T790M, then it is harder to know the best option. I do not think the third-generation inhibitors like Tagrisso and rociletinib have much proven activity in T790M-negative cancers. They have presented data that some patients do respond, but I suspect this is a failure of their testing to identify T790M rather than truly being negative.
For most patients without T790M, a very reasonable option is to stop the Tarceva and start traditional platinum doublet chemotherapy. Chemo can be very effective in EGFR-mutant lung cancer, on average more so than run-of-the-mill lung cancer. There is no advantage to continuing the Tarceva or another EGFR inhibitor if the switch to chemo is made, a large phase 3 trial called IMPRESS proved that last year.
Afatinib by itself is not effective once Tarceva loses effect, but the combination of afatinib and cetuximab does have some evidence supporting it. This is not very easy though (lots of rash and diarrhea although manageable) and doesn't last very long (average 6 months) so I normally reserve this for after other options like chemotherapy have been tried.
Other clinical trials could be an option as well, such as combinations with MET inhibitors if the new biopsy shows MET amplification (present in 5-10% of cases).
Hope that helps!
Reply # - February 19, 2016, 01:17 PM
Hi Janine and Dr. Pennel,
Hi Janine and Dr. Pennel,
Thank you so much for the information. It really helps.
Reply # - February 19, 2016, 01:19 PM
I would also point out that
I would also point out that blood tests for T790M are reliable if positive, but are not very sensitive so a negative result is not always correct. The "gold standard" for T790M testing would be to biopsy one of the areas that is progressing and test the cancer tissue itself. This is not always possible or practical, and if the blood test is positive is not necessary, but is something to keep in mind if the result is negative.
Reply # - February 19, 2016, 01:39 PM
Yes, that is what my
Yes, that is what my Oncologist suggested as well. If the blood test is negative, he suggested a needle biopsy on the primary tumor.