after loss of t790M as resistant mechanism - 1294500

Hi Kempten,

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.

JimC
Forum moderator

I may be wrong but considering its bleeding issues I don't think avastin is meant to be penetrate the bbb.
Jim? onthemark?

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?).

Janine

Hi Kempten,

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.

otm

Hi Kempten,

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.

HI Kempten

I agree with your suggestion that blood biopsies ought to be taken to accompany tissue biopsies due to tumour heterogeneity, and hope there are other clinical trials that open up for you to participate in.

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 SBRT.

What do you think of the bill that was recently signed into law called "Right to Try"? Are you in the US?

Also, medical cannabis 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.

I agree with your suggestion that blood biopsies ought to be taken to accompany tissue biopsies due to tumour heterogeneity, and hope there are other clinical trials that open up for you to participate in.

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 SBRT.

What do you think of the bill that was recently signed into law called "Right to Try"? Are you in the US?

Also, medical cannabis 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.

Hi Kempten,

I agree with your suggestion that blood biopsies ought to be taken to accompany tissue biopsies due to tumour heterogeneity, and hope there are other clinical trials that open up for you to participate in.

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 SBRT.

What do you think of the bill that was recently signed into law called "Right to Try"? Are you in the US?

Also, medical cannabis 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.

Kempten,

I agree with your suggestion that blood biopsies ought to be taken to accompany tissue biopsies due to tumour heterogeneity, and hope there are other clinical trials that open up for you to participate in.

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.

What do you think of the bill that was recently signed into law called "Right to Try"? Are you in the US?

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.

Hi Kempten,

Dr. West has a detailed talk about some aspects of your situation here.

It's called

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.

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

https://www.mdedge.com/oncologypractice/article/129890/lung-cancer/nivo…

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.

kempten,

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.

JimC
Forum moderator

Hi Kempten,

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)

" at https://www.youtube.com/watch?v=YrPw5dvq3rc

"

My Top 5 ASCO 2018 Abstracts in Advanced NSCLC (BMIC-036)

" at https://www.youtube.com/watch?v=R8xyNpgr_mY

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.

Hi kempten.

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:

The role of p53 in cancer drug resistance and targeted chemotherapy

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.

scohn

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.