I can't thank you enough for the service you provide!
This is my second topic here but I do not know if the information I provided earlier under another topic is still available to you, so here it is...
59 year old female, never smoker
Diagnosed with NSCLC stage 4 (4 brain mets) in March 2013
Cyber Knife to brain mets days from diagnosis
EGFR+ (Put on 150 mg Tarceva since April 2013)
3.5 cm Lung tumor from 7.6 SUV to 1.9 SUV and brain mets gone by November 2013
URL removed through VATS on November 2013
Surgical pathology: still EGFR+, C-MET amplification, live cancer cells found in 9 out of 30 mediastinal lymph nodes upon surgery
Radiation to the mediastinum not recommended
NED from the neck down since VATS
A 4mm focus of enhancement found in the brain on December 2014 and gone
NED from head to toe
Started monitoring CEA two months ago (1.5 twice) (No baseline at time of diagnosis)
A recent liquid biopsy indicates no other mutation, but NF1 (.48%) (99.52% no mutations)
Currently, on 75mg Tarceva and fully functional
1. Have you seen other cases similar to mine? Can EGFR and C-MET just disappear? I learned from your videos that liquid biopsies have a 60% sensitivity. Can this mean that there is still a 40% chance I could still have EGFR and C-MET?
2. If these results are to be trusted or may resurface in another liquid biopsy, should I stop Tarceva or reduce
the dosage? If Tarceva is what is keeping me NED and I do not have evidence of resistance, should I stop it as to not lose a life line if and when I have progression?
Your opinions and comments will be greatly appreciated!
Wed, 07/22/2015 - 14:38
It's so good to hear you're doing so well! I think I can handle these questions but don't know that I can come up with quotes from previous threads and blogs, videos, etc...time restraints.
1. Yes, just as tissue biopsy isn't 100% accurate neither is the serum test. So far they have shown to be around 60% accurate, which means 40% of the time they miss something. This translates to, if a mutation is found (happens 60% of the time there is a mutation) then there's a mutation, if it isn't found there may or may not be a mutation (happens 40% of the time when there is a mutation and 100% of the time when there is no mutation).
2. If there is thought to be cancer then continued treatment with a treatment that isn't causing difficult side effects is continued. So this is where is gets murky, if you stop treatment and the cancer shows itself it's possible that the same treatment may no longer work. But you won't know if you don't stop treatment.
One thought is someone could wait until there is a 3rd generation EGFR tki available before stopping treatment for a close watch and see. That way there will be a good alternative if tarceva didn't work if you needed it. On a personal note this is what happened to my husband and he was one in over a hundred or more who hasn't recurred. He been off treatment for 3 years and NED for almost 4. Also his treatment side effects were becoming increasingly difficult to maintain.
I hope you're NED for years.
Wed, 07/22/2015 - 18:42
Thank you, Janine, for your prompt response and the way you clearly explained how sensitivity in liquid biopsies works.
Now, I would like to address further the following comment:
"If you stop treatment and the cancer shows itself it’s possible that the same treatment may no longer work."
Does cancer tend to change after treatment stops? I thought it was more likely for cancer to change in response to treatment. My concern is that being on Tarceva for an extended period of time will most likely bring about some sort of resistance sooner than later, thus, completely eliminating it as a treatment option for me.
I guess my question is: Which is the lesser of two evils?
Thank you for your follow up response!
P.S. Janine, would it be possible to get other doctor's opinions on this? Dr. West, perhaps! I don't think there is any consensus in this area...
Thu, 07/23/2015 - 07:19
Although I certainly hope not, it is possible that your cancer is becoming resistant to Tarceva right now. If it is, and you stop Tarceva, you would soon see evidence of progression. You would not know whether that progression is due to resistance to Tarceva, or because you stopped a drug that was keeping it in check. The only way to find out would be to restart Tarceva and see if it again successfully holds your cancer at bay.
As far as your cancer eventually becoming resistant to Tarceva, cancer can and does often become resistant after a period of treatment, but sometimes it does not. There are patients who successfully treat their EGFR positive cancer for a number of years with an EGFR TKI. For whatever reason, their cancer does not mutate in such a way as to become resistant.
I think of such treatment as a detour sign on a road. If you come across one, you are likely to turn and take another route. But you don't have to - you could just stop and sit there. So strictly speaking the roadblock does not cause you to turn, it just gives you a very good reason to do so. In that sense, Tarceva may not cause a cancer to mutate, it just provides circumstances which favor mutation. How and why that happens isn't clear, although we know that in most instances that's what happens.
I hope your cancer continues to stare at the Tarceva "sign" with no clue what to do!
Thu, 07/23/2015 - 08:15
Thanks for that explanation Jim!
Thu, 07/23/2015 - 13:21
Thank you, Jim! Once again we have very clear explanations!
As far as the following comment:
"...cancer can and does often become resistant after a period of treatment, but sometimes it does not.,"
Then, asuming we could give some reasonable validity to the idea that I am in remission and I am not experiencing resistance yet (clear scans, CEA = 1.5 (twice), liquid biopsy showing NF1 (.48%), 99.52% (no mutations)), would it not make sense to stop treatment before my cancer finds a detour? We could continue monitoring with scans, blood markers, and liquid biopsies, until some kind of trend or elevation would become evident. At that time, based on the findings of EGFR or any other targetable mutations, I could start from scratch buying some additional time before the cancer would find another detour. I am thinking that especially with resuming Tarceva after some reasonable break, the cancer might react as if it has never been treated with it and it may take a long time again for it to figure out a detour, if any.
I am aware that there is no data to support whether stopping Tarceva before apparent resistance will ensure longer term effectiveness the second time around, but I have been hoping there would be some kind of personal experience with patients who have stopped before progression as to not lose a life line later, in case they would remain EGFR+?
I give you both a big thank you and I hope you can continue to share your knowledge and impressions as they relate to patients in my predicament.
Have a great rest of the day!
Fri, 08/07/2015 - 18:28
I can offer my husband's experience. He has liver progression after 4 years on crizotinib. A tissue biopsy confirmed metastatic adenocarcinoma. The tissue was sent out for mutation testing to assess for original ALK mutation and after 4 weeks we were told there was not enough tissue for the testing so a liquid biopsy was performed. About a week and a half later we got the liquid biopsy results that did not show any mutations. We were very confused and quite frankly scared to death as by this point he had switched to ceritinib and had been taking it for six weeks. We were trying to decide with our oncologist what the next step would be ( re biopsy versus wait on scan) when lo and behold a tissue biopsy lab report showed up from the liver biopsy confirming ALK mutation...turns out they had enough tissue to test for ALK after all. So here we have a positive ALK on liver tissue and negative on serum... I it is all very scary but I always tell my husband that the proof will be in the scans...