I have been off Alimta maintenance for about 1 1/2 months now and recovered a little from pretty
severe side effects . The chemo lasted me for about 6 months before progression .
Better than nothing .
A recent biopsy shows loss of t790M as my only resistance mechanism .
I'm still on Tagrisso
The next treatment will likely be another chemo. I have had a terrible time on Carbo/Alimta and am
very reluctant to try another one .
Does re-challenging Tarceva ever make sense in such a situation ?
How about adding Avastin to my treatment .
I'd rather try anything else than another chemo.
A single new brain met will be irradiated soon , other that that I have some progression in the lung .
Thank you again for your advice
Wed, 05/30/2018 - 07:09
I'm glad to hear that you're feeling at least a bit better. For most people, Alimta doesn't cause such problems, especially as a single agent for maintenance, and I'm sorry you're one of the few that really struggle with it. I understand your reluctance to move to another chemo agent, although it's certainly possible that your body has a particular problem with Alimta in particular, and that other agents might not be anywhere near as toxic for you.
Returning to Tarceva is probably not that attractive an option since you're already taking Tagrisso and you progressed on Tarceva previously. I don't see what Tarceva would do that Tagrisso isn't already doing; cancer cells that seem to be resistant to Tagrisso would likely resist Tarceva as well. In general, there is reluctance to return to a drug on which a patient progressed initially.
There's not a great deal of evidence to show that Avastin adds much in the maintenance situation, although it is usually pretty well tolerated so you could try it and see if it halts the progression.
As you probably already know, EGFR+ patients have a low response rate to immunotherapy, but if your cancer shows high PD-L1 expression, that could be another option.
In one of your previous threads, the idea of a treatment break was discussed, since the progression at this point appears slow. In your case, that might mean continuing Tagrisso without adding a new agent (assuming that you are tolerating Tagrisso well), or you could go off treatment (even if just for a month or two) and let your body rest from the rigors of anti-cancer treatment. A full treatment break can also help your frame of mind. Of course, close surveillance clinically and with follow-up scans would be necessary in order to detect any change in the pace of progression.
In such a situation, there's no clear choice; all that can be done is to weigh the options and move forward. I hope you can find an option comfortable for you.
Wed, 05/30/2018 - 12:41
Thank you Jim for your advice
I will likely not rush right into the next suggested chemo and try to put on some weight first .
Even though dexamethasone is rough on the system , after my upcoming SRT I asked to be put on it for a few days to gain back some weight .
My appetite is at rock bottom and never recovered after chemo . Any thought of food fills me with disgust
and I have to force myself to eat anything .
We can assume I guess that the next chemo will not penetrate the blood brain barrier ?
That's why I was wondering about avastin . But I heard like you mentioned, that it does not seem to be terribly effective .
Wed, 05/30/2018 - 17:52
I may be wrong but considering its bleeding issues I don't think avastin is meant to be penetrate the bbb.
Have you been able to find a liquid nutrition sub that you can drink? We tried all sorts of products and found Don could take vanilla ensure plus, publix supermarket sold a twin at half the cost but only off and on. Generic magace may help with appetite as long as your tumor burden is relatively low, it worked wonders for Don.
Once you catch your breath gain some weight off chemo a single agent may not be as nasty as you fear it may be (easy for me to say...right?).
Thu, 05/31/2018 - 06:39
I assumed Avastin might penetrate the bbb because it was approved for glioblastoma , but I heard
from several people now that it is not that effective when added .
thanks for your suggestions on liquid nutrition . The other stuff I'm not familiar with . It's a man made form
of the hormone progesterone ?
I started drinking high protein Ensure and I force myself to eat albeit with zero joy .
My biopsy came back with a couple of non actionable mutations which both might make my cancer more resistant to therapy .
an excerpt from a study :
" In conclusion, we observed that c-MYC gain was associated with lymphatic invasion, and was an independent poor-prognostic factor for DFS and OS in lung adenocarcinomas, both in full cohort and stage I subgroup, and possibly for DFS in EGFR-mutant subgroup. "
The other one was a tp53 R273C mutation .
I'm seriously wondering weather doing nothing might give me the better quality of life for now ?
Thanks so much for answering
Thu, 05/31/2018 - 08:02
I read the same as you about Avastin being a treatment for gliobastoma and also, if I understood correctly, that it might help other drugs penetrate the blood brain barrier but I haven't seen anything so far that jumps out for effectiveness in lung cancer brain mets. It does not appear to have an adverse safety profile for patients with brain mets compared to those without.
There is also a thread on inspire about concomitant use of Tagrisso and Avastin in lung cancer here: https://www.inspire.com/groups/american-lung-association-lung-cancer-su…
Regarding immunotherapy, have you been tested recently for pd-l1 and tumour mutation burden? Even if it is a long shot it might be worth testing for.
There are some other drugs besides dex that have weight gain as a notable side effect and might be less harsh on the system. As well there are appetite stimulants like Janine suggested that can have a positive effect.
I saw on a previous thread you were contemplating a clinical trial. Is that still an option?
You have had a long struggle and I admire your perseverance and courage.
Thu, 05/31/2018 - 09:07
Thank you for responding .
I did a tissue biopsy at Mass General in Boston to try to get into a clinical trial for Tagrisso combined
with Savolitinib .
For me to be accepted I had to be MET positive . Unfortunately I was MET negative . So no trial for me .
I'm always wondering when a trial demands a tissue biopsy, how representative this biopsy result is considering
only a single site is biopsied .and other sites with possibly more diverse heterogeneity are missed .
They should always do a companion liquid biopsy and compare tissue to liquid in my humble opinion .
Astrazeneca I think did this just for their own research but the results are kept from trial doctors and patients .
That's what it said on the forms I had to sigh for consent
My guess is that my mutation load is very low and it would be highly unlikely to make a successful
try with immunotherapy.. I will have to ask my local doctor if PD - l1 was tested tor .
I will see him today.
I will also ask for appetite stimulants . I just know that dexamethasone makes me eat like a horse
and I do have an upcoming SRS of a brain met . We could kill to flies for the price of one
Thu, 05/31/2018 - 14:50
I agree with what you wrote about tumour heterogeneity and getting a blood biopsy in addition to the tissue one. Hopefully other trials will come up that you can participate in.
It's great that dex makes you eat like a horse. Maybe that is enough to kick start your appetite. I also lost my appetite for most of the day after chemotherapy but find I can eat more in the evening without much effort. Have you thought about trying medical cannabis to see if that has an effect on appetite as well? It can paradoxically cause some people to get nauseous and lose appetite but for others it can be remarkably effective.
Ask your doctor about your 'tumour mutation burden (TMB)', in addition to PD-L1 which I read also has prognostic significance for response to immunotherapies. Again it is a long shot but worth asking for.
What do you think about the bill that was just signed into law called "Right to Try"?
I hope your upcoming SBRT is as effective as your previous treatments.
Thu, 05/31/2018 - 14:57
Thu, 05/31/2018 - 14:58
Fri, 06/01/2018 - 06:53
Fri, 06/01/2018 - 06:55
It's great that dex makes you eat like a horse. That might be enough to put you back into a frame where eating is an enjoyable habit rather than a difficult chore. I hope you have success with your upcoming SRT.
Also, medical marijuana can be a godsend for some cancer patients who want to build up their appetite. I also lost mine after chemotherapy, but find it is better towards the end of the day and in the evening.
Fri, 06/01/2018 - 10:00
I'm conflicted when it comes to the " right to try " legislation
This statement ( not from me ) kind of mirrors how I feel about it :
Michael Becker, a former biotech executive who is dying from cancer, told NPR's Scott Simon in February that he opposes "right to try."
"The problem becomes that you have a lot of false hope as a terminal cancer patient. You want to cling to anything that's going to sound like it's an opportunity to live longer or have a better quality of life," he said. "That hope can sometimes cover up the realities of some of the more sinister aspects of getting a drug, which are things go wrong. So I could take a drug that was purported to help me, and it may actually make my condition worse."
I saw my local onc yesterday . He wants to put me on Taxotere indefinitely. I might decide not to treat any further
at this point, except for the occasional local ablation therapy to relieve symptoms .
I read some patient experiences with this drug that did not seem to increase quality of life as a
4th line therapy .
I might change my mind later but right now I have a better quality of life doing nothing .
Sat, 06/02/2018 - 07:25
Dr. West has a detailed talk about some aspects of your situation here.
Treatment Options for EGFR T790M Negative Acquired Resistance
It makes sense that you would not want more chemotherapies but I do wonder if other medications might be considered in your situation. It's almost a half an hour talk and there is more information in it than I can understand at the moment but it may be helpful to you if you haven't already heard it.
I also have mixed feelings about Right to Try. There will be some patients who will turn out to benefit from it. The question is how many and also how much suffering it might lead to. Hopefully in the law there is at least a way to record the single person trials to build a national database of both positive and negative results.
Sun, 06/03/2018 - 18:21
Thank you so much for making me aware of Dr West's Video
He is stating one of my
dr's trials in this video . I think it's from Jan 2016 ? I think my progression would
warrant systemic therapy at this point but I'm just not very good at withstanding it ( chemo ) . The response rate would be around 17% in my case I was told . So pretty low .
I will wait and see what happens . In either case, the brain would remain unprotected and we are still relying
on Tagrisso and SRT for the brain . Not sure how effective Tagrisso is at this point but I hope it's
better that discontinuing .
Sun, 06/03/2018 - 19:23
I wouldn't want to go on Taxotere either.
Have you recently been tested for PD-L1? There's evidence that PD-L1 expression can change when cancer cells develop TKI resistance (see the review paper below). Also, Opdivo can work even with low expression. See for instance:
Nivolumab effective in PD-L1–deficient lung cancers
There's a 2018 review paper:
Osimertinib resistance in non-small cell lung cancer: Mechanisms and therapeutic strategies
that has a ton of detailed information but unfortunately it is behind a publication wall. I could cut and paste and send it to you but I am not sure the best way to go about doing that.
Wed, 06/06/2018 - 14:01
thank for the recent opdivo suggestion. I will revisit this again with my oncologist .
I also have a low level of autoimmune disease . I was always afraid opdivo could make this much worse
My immune system is not completely normal . I have chronic fatigue immune dysfunction syndrome,
low grade psoriasis and interstitial cystitis . Non of these diseases have been officially classified as
autoimmune diseases except for psoriasis but I'm very afraid of a major flare up if I try this .
Historically flair ups coincided with allergies, infections, stress , whenever the immune system is up -
Interestingly chemo therapy with its immune compromising side effects got me into a partial remission
for all of these immune related diseases .( chronic fatigue better , cystitis better , psoriasis non existent .
I'm also trying to follow the ASCO discussions closely
Wed, 06/06/2018 - 19:23
Lots of good information here. One thing to remember, though, is that when response rates are quoted, that rate includes only patients who achieved significant tumor shrinkage. Especially for later lines of treatment, that kind of shrinkage is not common. As Dr. West points out in the video, more relevant is the disease control rate, which also includes patients whose cancer remains stable, a result that is quite good for heavily-pretreated patients. In addition, with such patients there is more variability - some patients may have more significant or widespread progression than others, so the results will tend to be more variable as well.
Wed, 06/06/2018 - 19:53
Jim's point is a critical one and I'll be sure to remember if I ever have to cross that bridge. I'm also trying to follow the ASCO discussions. It would be nice to have a book club to compare notes one day on all the new developments in lung cancer treatment. I also understand your reservations about immunotherapy. Your situation suggests that some may do better with fewer symptoms on chemo and immuno than just immuno... well at least that is a theoretical possibility.
Dr. West has some videos on youtube under the name of "Beacon" which have a lot of useful information in addition to his videos here. Two that I can recommend are
Is immunotherapy ineffective for driver mut-pos. advanced NSCLC? Time to walk that back. (BMIC-027)
My Top 5 ASCO 2018 Abstracts in Advanced NSCLC (BMIC-036)
Thu, 06/07/2018 - 14:29
https://twitter.com/lcsmchat is a wonderful twitter feed and abuzz with asco chatter. I wish I spent more time there but you're all right now is the time of sharing and I'm going to check it tonight. Dr. Pennell and West are both followers/ing. Is the monthly chat discussion still going on? It's a great tool for open dialogue of lung cancer care.
Fri, 06/08/2018 - 09:06
I am so sorry to hear about your recent issues in resistance. I too have been a great admirer of your strength and courage.
I wanted to just add a brief thought from the cell biology side. If I understand from what you said above, you have developed a tp53 mutation. This protein is involved in DNA repair and destruction of overly damaged cells. Since carboplatin is an agent that works by damaging the DNA of cancer cells, tp53 mutations often have resistance to carboplatin therapies and others that work on DNA directly. It also seems to sometimes have an effect on the effectiveness of EGFR targeted therapies. See for example:
That is most likely why they want to switch to Taxotere, which is a therapy that works by a completely different mechanism, working to physically hinder cancer cells from undergoing cell division by altering cell structure (not the DNA). That is why the effectiveness, and side effects, of Taxotere are often different from the carbo/cis/alimta type treatments (although digestive issues are often a major side effect).
I am certainly not advocating for whether or not you should do the Taxotere treatments, but I just wanted to let you know that the treatments work in a very different way from the chemotherapy you were on.
I wish you all the best as you make your way through the treatment decisions, and for healing of body and spirit.
Fri, 06/08/2018 - 10:44
Thanks for replying
My recent tissue biopsy showed a c-MYC gain also. Not sure if this makes a forth line chemo even less likely to respond ????
My primary issue is deciding what gives me the better quality of life right now .
Chemo mostly makes people feel worse and sometimes absolutely miserable . There is usually for many
a light at the end of the tunnel . You fight through the chemo and then things get better .
This will not be the case here .
Also what to do with Tagrisso ? Would Tagrisso interfere with the Taxotere ? Would discontinuing the
Tagrisso cause a flare of progression in the brain ??
I remained on Tagrisso during my Carbo/Alimta therapy . Did it make the carbo/alimta less effective ?
I don't think so.
So many questions .
I'm just happy right now to have a somewhat enjoyable summer without too much pain ( sciatica in both legs )
but some balance problems and slight vertigo ( early lepto ?) Wondering about this too.
Nothing has shown up on MRI jet .
Taking on day at a time
Fri, 06/08/2018 - 11:21
Thank you Janine for the twitter feed and scohn for sharing insight on mutations and chemotherapies.
I'd probably do the same as you, Kempten, and stay on Tagrisso. My impression from watching videos of Dr. West and others is that some patients too early abandon targetted treatment where the few places the cancer escapes can be controlled with added local therapy. I don't recall the specific videos unfortunately.