Adjuvant Immunotherapy research with curative intent - 1271667

amy3375
Posts:16

Hi, I'm interested in particular to see release date of "Mid-2016 – MK-3475 for PD-L1-positive NSCLC" in the calendar . I wasn't able to find this or any additional information elsewhere. Do you know if this is still the case?

Meanwhile my Dad is considering joining this

Does the pending approval give more confidence in the effectiveness of Pembrolizumab? And if yes, does it also mean the trial would be likely to be cut short? Maybe the point of this study is to look at this new drug used with the standard concurrent treatment irregardless of PD-L1 status and there would be no impact.

While I know Dad has the EGFR-19 marker I don't remember any mention of PD-1 or PDL1. Seems like he needs to find out and weigh whether the TKI strategy would be a better bet. All of this stuff is so new. Exciting times I guess!

I'm catching up on reading and educating myself (thank you GRACE for being here!!) so if anyone on this thread has suggestions of particular articles I would welcome that guidance. He has an appointment next Wednesday 11/4/15 with the PI and my goal is to equip him with some good questions.

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catdander
Posts:

Hi Amy,

pembrolizumab, brand name keytruda has been approved for 2nd line therapy. Many people are calling it by its brand name keytruda for the simple reason pronouncing pembrolizumab is pretty hard to get a handle on :)

It sounds as if the phase II trial with concurrent chemo/rads is targeted at curing the patient. If you do a search on grace for stage III treatment your find some people who are healthy enough are treated with a platinum doublet and radiation. It's a tough treatment but may be worth it if if a cure is the final outcome. Sometimes radiation is given first then chemo, it's less toxic but also may be less effective.

Your guess is right, the trial is to see what happens in a curative setting for keytruda. That's a typical path for cancer research to take. While the data shows people with non-squamous nsclc with a higher number of pd-l1 do better than those with a lower number, but all have shown efficacy.

On a personal note, my husband was diagnosed 6 years ago with stage III inoperable nsclc (2 subsequent mets upstaged him but never were able to get positive biopsy on mets so who knows maybe was always stage III.) He received concurrent chemo/rad that may have cured him because he remains NED 3 years post chemo and 6 years post chemo/rads. It's a hellava road but we're both glad for the outcome.

Keep us posted and don't hesitate to ask as you go.

Janine

P.S. I'm going to move your post to make a new thread because it holds it own weight. Let me know if we need to change to title.

amy3375
Posts: 16

Janine,
I really appreciate your reply. Thank you for translating the drug names and teaching me the phrase "curative intent". Cautiously hoping to have a similar outcome as your husband. Just have to put one foot in front of the other. I may be states away, but I am on the journey too. I second your statement that the platinum chemo with radiation is tough. How we take for granted being able to swallow...

Sorry about my clumsy use of the site. I tried to use the HTML tags and it just got worse when I went back to fix them. Now I see the buttons at the top which I'll try another time.

I sent dad a list of questions for the PI which I compiled after reading and exploring on this site. Now I'm seeing additional angles like the cost which I didn't even touch... It will be interesting to learn whether he will be tested for PD-1. If he was already I missed it. Seems unlikely.

I will post again once I learn whether he is committed to the trial or not.

p.s. Since this thread is now about immunotherapy research I'll include a marketing type link to a trial in PA http://www.uphs.upenn.edu/news/News_Releases/2015/02/bauml/ I am not sure if this would be considered as having curative intent. There is probably a way to find other similar studies. I'm just sticking with the one Dad qualified for. I did appreciate the PA press release for speaking in regular English as the jargon is still new.

catdander
Posts:

Amy,

I'm glad we can be of help. As the sub title suggests "definitive therapy" it is focused on a cure.

One of the trials that hasn't been able to accrue enough people is one that pairs surgery against chemo/radiation for curative treatment. Most people will choose surgery over radiation given the choice (if the tumor is reachable, patient is healthy enough that sort of thing). So it's impossible to know how chemo/radiation stacks up to surgery.

Although this trial isn't set up to measure surgery over radiation it does give people like your dad the chance for curative treatment that otherwise might not be an option. I don't think his pd-l1 numbers really matter especially if he's already been accepted.

I look forward to finding what he chooses to do.

Janine

amy3375
Posts: 16

Just a quick note - I don't see the subtitle you mention and a word find for definitive came up empty.
When I go here https://clinicaltrials.gov/ct2/show/NCT02343952 it says the purpose is treatment and that they will measure safety and tolerability as well as Progression Free and Overall Survival with a time frame estimate 18 months. Now I have to refresh myself on how 18 months compares to the wait and see option with the current standard of care...

catdander
Posts:

Amy,

The wording, definitive therapy is in the news brief here, "NEWS BRIEF FEBRUARY 3, 2015
Penn Medicine's New Immunotherapy Study Will Pit PD-1 Inhibitor Against Advanced Lung Cancer

For first time, researchers will investigate PD-1 after definitive therapy in group of lung cancer patients" http://www.uphs.upenn.edu/news/News_Releases/2015/02/bauml/

As long as a nsclc is contained in just one lung it can be curable; one type of curative treatment often available to stage III nsclc is radiation given at the same time (concurrent) as a platinum doublet chemo. It appears that the trial wants to test whether or not adding immunotherapy after chemo/rads will give this group of people a better chance of cure. All trials set some arbitrary measuring points, this trial has set 18 months to see if the cancer returns. That's most likely because if the cancer is going to return it will within 18 months.

Some info for thought: Radiation in this case is to kill all the cancer, however studies have shown that adding chemo definitely adds several percentage points to the overall chance of cure. It's not understood what's happening but it might be that there are a few rogue cancer cells that sometimes gets cleared with the chemo or maybe the chemo adds radio sensitivity to the tumor.

The researchers are hoping that adding more will do more.

Does this help answer your questions?

Janine

amy3375
Posts: 16

Yes, I'm sorry I confused the issue. Dad is looking at a study run by the Hoosier Oncology Group in Indiana which I was only comparing to the Pennsylvania study in a post script above. The PA press release I found when looking for more info on the drug and it was easier for me to read- probably was for you too! Sorry.

Hoosier
https://clinicaltrials.gov/ct2/show/NCT02343952

Penn
https://clinicaltrials.gov/ct2/show/study/NCT02316002

catdander
Posts:

Please don't apologize for anything you've said while learning this crazy difficult subject in such a stressful time. Don't forget cancer is used as a figure of speech to explain most any impossible situation. As long as we can find our way to the understanding we're looking for. :)

amy3375
Posts: 16

Update:
Dad committed to joining the Hoosier trial and had the first dose on Tuesday. So far I haven't heard of any side effects.

Interesting that they did require access to refrigerated tissue samples in order to test for the PD markers. Dad was puzzled when they said he would be admitted either way given his understanding of how the drug is supposed to work. It does seem pretty murky given the simple PD-1 inhibitor explanation on the one hand, while on the other hand people without evidence of the marker also do well as you mentioned. He pressed to find out more and basically got an "it's complicated" response. A good reason to do trials I suppose.

It could be the tests are unreliable or that there is more to the story of how the drug works or something else. Dr Garon says here
http://cancergrace.org/lung/2015/11/1/gcvl_lu_pdl1_immunotherapy_biomar…
that "the way drug development currently is, one essentially gets credit, additional credit, for developing a biomarker along with the drug" which I interpret as a financial incentive for drug companies. Follow the money.

I don't think they will be sharing the tissue staining results with him. I've reached the point that I would rather not know in order to give my mind a rest from the guessing and betting on his chances. We don't know the future and statistics don't guarantee one person's outcome. I'm grateful that my folks are just an hour from an academic health center and that he has the option to join a trial for second line treatment while living at home. Simply waiting and hoping would have been nerve wracking.

This new milestone means I get to update my signature lines. Wish us luck!

JimC
Posts: 2753

Hi Amy,

Thank you for the update. The value of PD testing to predict response is not clear. As Dr. Solomon said in a recent GRACE video:

"I think what’s clear is that PD-L1 does enrich for a group of patients that are more likely to benefit. But I think what’s equally clear is that, if a patient is PD-L1 negative, there’s still a chance that they can benefit from treatment with a PD-1 or a PD-L1 inhibitor. So, this strategy of using PD-L1 to enrich for a group of patients who might want to, for example, use a PD-1 axis inhibitor for the first line, probably does make sense, but it probably doesn’t make sense to exclude a patient based on PD-L1 negativity..." - http://cancergrace.org/lung/2015/11/11/wclc_2015_order_pd-l1_testing_be…

Good luck and best wishes for a great response to the trial regimen.

JimC
Forum moderator