Rebiopsy for resistant mutations following Tarceva - 1262372

katief
Posts:6

61 yo female, NSCLC,adenocarcinoma,EGFR, have done well on Tarceva for 18 mo, last PET/CT shows 2 lesions to the liver, numerous tiny nodules in both lungs, some noticed in peritoneum and omentum, I also have a node lighting up in the left breast near the axilla. MRI of brain negative.
It's time to change treatment. I am still feeling good, snowshoeing and maintaining weight. Labs are all good protein and albumin, kidney, liver, but WBC on the low side 4.0.- My new oncologist follows LC patients with CT only, -just changed Drs. - Needle bx done on node in breast to determine if it's mets or new breast CA.
Assuming just LC I think I should ask for testing to see what mutations are causing the resistance. ( Based on what I have read and watched here.) Do they bx the new Mets or the old tumor or both? Tumor is said to only be showing slight growth. What type of testing is best ie FISH? Is is too late for that testing to be helpful?

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JimC
Posts: 2753

The best testing method is to find out whether your cancer cells have activating or resistant EGFR mutations, done by gene sequencing. FISH (fluorescence in situ hybridization) and IHC (immunohistochemistry) have not been shown to be as consistently predictive of benefit from EGFR TKIs. As Dr. West has said:

"Though there is some evidence to support that being positive for EGFR IHC, FISH, and an activating mutation are all associated with a greater probability of benefiting from EGFR inhibitors, the evidence has converged on a consistent finding that patients with an EGFR mutation are highly likely to receive a very significant benefit from EGFR TKIs, while the trends are less strong and less consistent for those with a high EGFR gene copy number (or gene amplification) as measured by FISH, and the least clear and consistent results of all for EGFR status by IHC." - http://cancergrace.org/lung/2010/09/20/lung-cancer-faq-what-is-egfr-and…

You can test the old tumor, but testing the new metastases will give a better indication of what mutations are present in the actively cancer cells. Though there are no currently approved agents which target resistant mutations, there are ongoing clinical trials designed to test drugs which may do just that.

JimC
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katief
Posts: 6

Thank you, I understand that afantinib may be effective for T 790m if it is the resistant mutation, and that it is effective with an HER mutation as well? Is that correct? In which case could it still an option for progression? Katie

Dr West
Posts: 4735

At this point, it isn't the standard of care to do repeat biopsies and mutation testing for T790M or other mutations at the time of recurrence, because there is rarely anything to do with that information. A small minority of patients will have small cell lung cancer (SCLC), which will guide a change in recommended treatment (to chemotherapy for SCLC). Many trials of promising agents, such as CO1686 and AZD9291, which have clear activity in previously treated patients with acquired resistance to Tarceva (erlotinib), will require or at least request a biopsy, but both of those agents are associated with responses in patients with or without a T790M mutation. In short, there's no clear use for mutation testing in standard practice.

Although responses are seen in about 5-7% of patients who receive afatinib after Tarceva, there is no survival benefit with it. There's much more interest in afatinib combined with Erbitux (cetuximab), but this is not a standard treatment for acquired resistance at the present time.

Good luck.

-Dr. West