after Tagrisso resistance - 1291187

Hey Kempten, So good to see you!

There is heightened promise and even FDA Provisional Approval of carbo/alimta/pembrolizumab (keytruda) as a front line option. I don't think you've had chemo yet so that would apply to you (insurance may need some coxing). Dr. Jonathan W. Goldman wrote the following piece discribing this combo as his "new go-to first-line regimen for non-squamous NSCLC patients without targetable mutations." http://cancergrace.org/lung/2017/07/25/why-carboplatin-pemetrexed-and-p…

I'm going to leave it at that for now and we're get more info in a bit.

Again, so good to see you're doing well. Congrats on the cancer vaca. :)

Janine

Hi Kempten,

Glad to hear that you had a good time in Scotland.

I think your interpretations of both issues are correct. Although Dr. West doesn't think that the combination is a bad choice, at this point he is not convinced that there are sufficient data to justify evan a provisional approval. The history of results of clinical trials of new agents or combinations is littered with instances of improvements in progression free survival, especially when the small trial population is selected from a group expected to do well, only to find that longer follow-up and larger populations show less impressive results.

And though I wish that choosing a clinical trial was as easy as plugging your information into a computer program, it appears that for the time being it will remain a bit more cumbersome than that.

JimC
Forum moderator

Hi Kempten,

If you're considering the trial of Tesevatinib, the trial listing doesn't indicate any need for a new biopsy. That's not surprising, since it's not addressing any new resistance mutation. Other trials may or may not require a new biopsy, depending on the target of the tested agent, if any. Most trials do require brain mets to be stable, so if there is any indication the met is growing, it will need to be radiated prior to entry.

JimC
Forum moderator

Hi Kempten,

I'm glad Jim joined the conversation. I don't know why I didn't mention Dr. West's view on the subject of combo treatment with keytruda, I knew it was there. Perhaps that's why I said I'd leave it for now, but I wouldn't normally do that. Sorry for any confusion or misdirection.

From what I've read in several posts during the years from oncs and members is that inclusion/exclusion criteria are somewhat up to the interpretation by the oncologist at that location. Especially if it seems open to interpretation and one is otherwise a good fit.

Keeping in mind the trial wants to know if Tesevatinib reaches the CNS (Brain or LM) when 1st and 2nd gen TKIs didn't:
It appears the no srs to the brain applies to a brain met or LM that has appeared during treatment with EGFR TKI. You fit that. Your previous srs shouldn't matter. In another bullet in inclusion they say wbr is ok as long as is was some time back. I'd argue the same applies to previous srs. Yours was some time ago, right?
It looks like they're saying it's ok to have had osimertinib or rociletinib as long as one had (or still had) cns mets after going back to 1st/2nd gen tki. Meaning the tki worked systemically but not in CNS.
I'm confused what is meant by peripheral progression and am guessing it means other than CNS but that would mean the wording is weird. I guess they could mean peripheral lung. Lung cancer doesn't normally progress to peripheral nervous system so that wouldn't be it.
I think the last one in your post about minimally symptomatic brain mets is talking about whether or not one needs immediate treatment (radiation). Not whether or not you've had it in the past. That way they are letting as many people as possible participate as long as one can function long enough to see if Tesevatinib works.

I hope some of this makes sense.
All best,
Janine

I wasn't thinking about you being on tagrisso. If you wanted to join this trial you'd need to go back on tarceva for 2 weeks. That's a interesting twist to the study. That suggests in just 2 weeks you might have efficacy in the brain. I guess they just want to rule out the possibility of renewed efficacy to tarceva while those who are taking tagrisso aren't automatically excluded.

Well i'll be, I just noticed there are 3 inclusion/exclusion sets. One for each cohort.

kempten,

It is my understanding from talking to oncologist at SCCA that Tagrisso deals with both the orginal EGFR exon 19 mutation and the additional T790 mutation. So Tagrisso should remain effective even if there is no sign of T790 mutation any longer. I don't know if the insurance is willing to continue to pay for Tagrisso if T790 mutation no longer exist, but they should be willing to pay for Tarceva.

Wow that's a lot going on. I'm floored to hear about the theft, not surprised just not heard of a personal experience. Someone knew the box had drugs from a specialty drugstore I assume. If they know what they have where's the market? The price tag on each pill I assume is over a thousand to US insurance companies. Are there individuals who actually pay that price though? I hope the thief is caught. Keep us posted on what steps are taken in the process and good to know you aren't having extra trouble getting a refill. I doubt any on our onc faculty would have helpful info on how to avoid that but I'll ask. When Don took tarceva I picked it up at the specialty office because it was just down the street from my work. How about talking to someone, like the insurance adjuster for the specialty drug store about it?

Interesting to hear about egfr tki possibly having an analgesic effect. Don had a lot of pain issues associated with his pancoast tumor and I remember there was a time when he needed less pain relief meds than other times during his treatment. I wonder if that was while he was on tarceva. That would be good news.

I don't think lung cancer specialists have much hope that returning to tarceva after acquired resistance to tagrisso will have efficacy. However this belief comes from incidental findings, not from real data from a study. I read the inclusion rule to be more of a just in case rule, so not to muddy trial results.

A short video by Dr. Geoffrey R. Oxnard from Dana Farber talks about how much we don't know about how mutations work by sharing data on the plethora of mutations that are showing up after acquired resistance.
Too I believe I remember him saying the info come from study of blood not tumor tissue.
http://www.targetedonc.com/videos/acquired-resistance-to-osimertinib-in…

Keep us posted.
All best,
Janine

I believe orphan drug status have already been developed but at some point the testing stopped, someone else picks up the drug and that testing becomes promising, but don't quote me on that.

From the FDA, "Orphan designation qualifies the sponsor of the drug for various development incentives of the ODA, including tax credits for qualified clinical testing."
https://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesCondit…

It goes on the say, "The granting of an orphan designation request does not alter the standard regulatory requirements and process for obtaining marketing approval. Safety and effectiveness of a drug must be established through adequate and well-controlled studies."

It sounds like the designation is to get already developed drugs to be sponsored for testing but it's not for patients not in a trial.