Hello Grace Team -You may recall that my wife was diagnosed with egfr+,exon19 del, poorly differentiated NSCLC in September2010. She was on Tarceva until 12/2015, when she experienced two brain mets. We switched to Tagrisso from 01/2016 on the unconfirmed suspicion she wasT790M+. Then, she progressed with miliary micronodules in both lungs in May 2016. We switched to carboplatin/alimta in mid-May 2016 for 4 cycles and then alimta maintenance. We just learned this week that she has progressed again with more miliary spread in both lungs ("difuse inumerable" micro-nodules). We got a tiny fine needle biopsy from the one nodule outside the lungs. The path report is negative for any targetable mutation, and also indicates that the cancer is no longer egfr positive. We confirmed it has not mutated to SCLC. I have 2 questions:
1. Would it be unusual for a cancer to lose its egfr status?
2. We are considering that the path analysis is a false reading and that the cancer remains egfr+ and then rechallenging with tarceva and avastin. We are 5 months out after the use of a TKI. Is there a view on how long one should wait to increase the chance of success of a TKI rechallenge (i.e., how long does it take the cancer to again be sensitive to a TKI)?
Thank you so much for your fedback!!
Reply # - October 22, 2016, 06:16 AM
Hi Dan,
Hi Dan,
I'm sorry to hear of your wife's progression. With regard to the EGFR status, it is certainly possible that the biopsy produced a false negative result; the smaller the sample of tissue obtained, the greater the risk of an inconclusive biopsy. Since cancer can do just about anything and cancer cells mutate over time, it's possible they mutated away from the original exon 19 mutation. It's also possible that your wife's cancer was not homogeneous, comprising both EGFR positive and negative components, and that the cancer cells in that negative component are the ones that are progressing. If so, that might argue against returning to an EGFR TKI.
There's no specific time frame for how long to wait to rechallenge with a treatment, although normally you wouldn't go back to it until perhaps a year or so later, as discussed by Dr. Sequist:
"...we know that if you have a holiday from Tarceva, you can regain sensitivity. This has been reported in a number of different case studies. I think we’ve all seen patients like this. They came off of Tarceva. They cycled through a number of different therapies and then, after a year or more break with no EGFR inhibition, they circle back to the Tarceva. They try it again and had another good response.
In some cases, that can last several months. Often it doesn’t last as long as the first response. But it can be an actual durable response. There has been no study comparing these two strategies head to head: whether to stay on it or whether to give yourself a holiday in hopes that you’ll resensitize the tumor. I think if that would be a very difficult study to orchestrate." - http://cancergrace.org/lung/files/2011/04/sequist-qa-session-transcript…
The usual deciding factors are whether there was initially a long-lasting response, and whether the cancer progressed while on the former treatment.
JimC
Forum moderator