Slow Progression on Tarceva (Long-Term) - 1265000

dan@hp
Posts:18

Hello! It was so nice to meet the Grace team at ASCO... and now I get to use Grace after a long break. In short, my wife has been progressing very slowly on Tarceva, with one small spot in her right lung now having grown to 7mm x 9mm over 11 months. We just completed her annual PET, which confirmed that there are no other progressing sites at present :)..... and her brain MRI two months ago was clear as well. :) She has chosen to wait until her next CT scan in 3 months to decide on a course of action regarding this spot. Depending on the result, we expect to either (1) stay on Tarceva and zap it with radiation, (2) take a biopsy and apply to either the AZ-9291 or CO-1686 trials if T790M positive (if more than one site appears), or (3) possibly thread in chemo. It all depends on the facts at the time. My questions.... have researchers gained any insight regarding (1) the characteristics of T790M progression (fast, slow, multiple sites, limited sites, etc?), and (2) whether or not these new 3rd generation TKIs for T790M breach the blood/brain barrier?

Thanks so much!

09/2010 - DX Stage 4 NSCLC, Adeno, Poorly Diff, EGFR + (Exon 19). Primary tumor left hilar mass size of large peach (now gone after radiation and Tarceva); small peach sized tumor in ovary gone after hysterectomy in 10/2011; extensive breast bone met, two vertibrae mets, left arm and right hip bone mets are all sclerotic and stable; one small brain met (gone after Tarceva).

10/2010 - Prescribed Tarceva as first line... still on it. Dose reduced from 150mg to 100mg.

Forums

JimC
Posts: 2753

Hi Dan,

Lisa and I enjoyed meeting you as well.

As with many therapies, there seems to be limited indications that the new TKIs may penetrate the blood-brain barrier, but I don't believe there's solid evidence that they do so better than Tarceva.

As far as T790M progression is concerned, Dr. Oxnard has stated:

"It has been suggested that T790M is associated with more indolent growth characteristics and an overall favorable prognosis when compared to T790M-negative drug resistance therefore we tend to see it more commonly in slowly progressing lung nodules. However, even patients exhibiting aggressive symptomatic progression on an EGFR inhibitor can be positive for T790M. At present, the only way to determine whether T790M is present is to perform a new biopsy of the tumor, and to have this specimen submitted for repeat EGFR genotyping." - http://cancergrace.org/lung/2014/06/09/egfr-t790m-as-a-clinical-biomark…

Many oncologists are reluctant to cease Tarceva when the progression is slow and/or limited in scope,

We'll be hoping for good scan results in three months!

JimC
Forum moderator

Dr West
Posts: 4735

Great finally meeting you in Chicago, Dan.

All of the options you mentioned are very reasonable. If you want to read more about the various options, search for "acquired resistance" here to review many discussions of the topic.

I don't believe we have seen any results yet or have any knowledge of response to the newer, third generation EGFR TKIs in the brain. I would not presume they penetrate into the central nervous system without evidence that shows this.

Good luck.

-Dr. West