Starting Immune therapy PD1, PDL1 as Initial therapy for Lung Cancer, Why wait? - 1260757

bfarz
Posts:7

Hi, I hope some one can help me. I see that there is a lot of promising research is being discussed regarding immune therapy. Some comparing or hoping for results that were seen with Melanoma.
Doesn't it make sense to start the immune therapy earlier in the disease course? Common sense ( not that cancer follows common sense) follows that if this is the fight between the cancer cells and the immune system that the sooner you boost and direct the active immune response that there would be a better chance.
Even the simple Flu antivirals are told to be taken ASAP.
Why are the clinical trials that have such good response are being done on late stage advanced cases who have either developed resistance to targeted therapy or chemotherapy. So many of these patients are by then fatigued and must have a poorer immune system. Why not start with the treatment that may give the longest survival and if not responding then switch to Targeted therapy or Chemo?
I have some medical knowledge and I know little knowledge can be dangerous. I just was reading the history and patients experiences when Targeted therapy was just a buzz, and so many people were not given the opportunity to take advantage of it.
Can anyone tell me if there is a place that would include a patient who has stable disease on Tarceva and also give the patient one of the immune therapies such as PDL1 or PD1 immunetherapy?

Forums
Full Archive

Reply # - November 30, 2013, 08:43 AM

catdander
Posts:

Hi bfarz, Welcome to Grace and congratulations on your excellent response on tarceva!
I understand your question and agree that the place for the immune system to kick in is before there's a problem or as soon as cancer has shown itself. The reason the anti PD-1 and PD-L1 drugs aren't being used in beginning stages of treatment is as you say they haven't been shown to be better than what you're getting. At this time these new drugs are just very promising and haven't been proven to be better than the treatment you're on. Perhaps that will be studied in a trial or if it's approved for treatment.

You say a little knowledge can be dangerous but I say a little knowledge is an excellent start. I know what you mean though and it's why I've ended up as a moderator on Grace. This is the most trustworthy and accessible place I found when starting my internet hunt for learning about cancer.

Below is a series of video talks and q and a on clinical trials that will help you understand how they work and what direction researchers and patients would like to take changes in the system.
http://cancergrace.org/cancer-101/2013/01/06/clin-trials-ramalingam-pt-…
http://cancergrace.org/cancer-101/2013/01/18/how-are-clin-trials-develo…
http://cancergrace.org/cancer-101/2013/01/27/ramalingam-clin-trials-pt-…
http://cancergrace.org/cancer-101/2013/02/02/qa-with-ram-on-clin-trials/

Following is a brand new thread that you may want to help get going on the subject once you've learned a thing or 2...that will make you not only not dangerous but a front runner in the new direction in clinical trials. :) http://cancergrace.org/topic/does-the-clinical-trial-system-work-for-pa…

I hope this makes sense and is helpful. If not the links most certainly will.

Janine

Reply # - November 30, 2013, 02:44 PM

cards7up
Posts: 636

Being on Tarceva would put you at stage IV advanced LC. Are you not able to get into a trial? Ar e you in the US? I can understand the reasoning for trying it on advanced patients first to see if there's any way to help improve their outcome. And I also agree with Janine, that once these trials are done they may start trials for those at lower stages for all the same reasons. First is do no harm!
Take care, Judy

Reply # - November 30, 2013, 06:23 PM

Dr West
Posts: 4735

The problem is that you're making a presumption that immunotherapy is going to be the best treatment without any testing to show that. Yes, immunotherapy helps some people, it seems, but with a response rate of about 20-25%, that's far less than the response rate of 60-75% in patients with an EGFR mutation who receive an EGFR inhibitor or in patients with an ALK rearrangement who receive an ALK inhibitor. It may be that immunotherapy is more effective in a broad population as first line treatment than standard chemo, but that will be determined by trials that directly test the question by comparing these approaches head to head. In the interim, it could very possibly be harmful to bypass a proven treatment by giving a therapy that hasn't been shown to be as effective and certainly not shown to be superior to standard first line therapy.

Trials are looking at immunotherapy earlier and earlier in treatment, but it has not proven to be so overwhelmingly superior to everything we've ever seen that we should presume that it is better before doing the actual trials.

-Dr. West

Reply # - November 30, 2013, 09:38 PM

bfarz
Posts: 7

Dear Dr.West
First of all you are amazing.
Dr. West, I am amazed by you. How do you get the time to answer and comment on every question.

The reason I seem so assuming is because time is of the essence and going down the wrong protocol takes away from the chance of being on the right one.
2 years ago my dilemma was Chemo or Tarceva. The local oncologist including a good friend said Chemo is the way to go , it is the standard therapy. I went to the AACR conference in San Diego and all the researchers said Tarceva is the way to go for EGFR+ Adenocarcinoma. Also, when you listen to researchers, they say that the response rate is lower may be that most of the patients on these trials are already on 3rd or fourth tx protocols and sicker.
So, Here is my delimma now, 2 years later,

56 year old healthy Asian Female with EGFR+ Del 19, T790M(-), who has stable disease on Tarceva for about 2 years.
Now if she has any progression, what should she do?
1) Chemo +/- staying on a) Tarceva b) adding a second generation EGFR inhibitor such as Afanitib
2) Afatinib only
3) Clinical trial for third generation EGFR inhibitors like AZD92921 or CD-1686.
4) Clinical trials for Anti PD-1 and PD-L1 drugs, ( In the Trial for MK-3475, the ORR for tumors with PDL-1 expression was @ 70%). Does that mean a biopsy needs to be done?
5) Clinical trial for Vaccine
and with options 3-5, are there trials that would allow combination therapy?

I know that I have to do a lot more research. I will attend the AACR-IASLC conference in San Diego.

I really appreciate all of you and also you, Dr. West. You guys are all just amazing to give people a place to think out loud. Who knows, these forums not only is compassionate but also so scientific. Cancer is so different., You just want to fight it with all you have and throw everything at it, hopefully something will do the trick. Its just that there is limited time so I am looking to find the best thing to throw at it.

GOD Bless All

Reply # - December 1, 2013, 01:22 PM

Dr West
Posts: 4735

I wish I could give you an answer about which path to pursue, but you probably know that all of these are reasonable choices and that there is no remote consensus of a "best" path to take. We can speak to what the evidence tells us, but we don't like to just speculate when there is no evidence to speak to the best approach to pursue.

While I do understand the temptation to treat with everything as soon as possible, we don't have so many effective treatments that we favor doing more than is needed at any one time to control the cancer. In general, I don't favor starting new treatments preventively, when it might well do a lot more good later, when cancer progression provides a more compelling need. Also, any cancer treatment, including immunotherapies, can have significant side effects (I've seen some from immunotherapy that landed a patient in an ICU, and occasionally they can be fatal), so we want to be very judicious about giving an unneeded therapy with the potential for serious side effects, even if that potential is limited.

-Dr. West

Reply # - December 1, 2013, 05:37 PM

ssflxl
Posts: 204

Bfarz

I am at the point that you are at. I have been on Tarceva for 3 years now - had a couple episodes of cyberknife to some small growth. Now I am symptomatic with some neuropathy and at a point that I can't get anymore cyberknife. You are correct about the choices you listed. However, in the end, there are trials that we won't qualify for so we don't really have that many choices to choose from.
Afatinib is not necessarily much better for Tarceva resistant patients and has more side effects.
Most if not all clinical trials with immunotherapy require that patient had failed chemo, and I have never been on chemo.
I am waiting for repeat biopsy to test for T790M to see if I can qualify for the CO 1686 trial at Stanford.
If I don't, then I will do chemo, which is probably not the worst

Reply # - December 17, 2013, 05:48 PM

wantvictory
Posts: 16

I have had Carbo/Alimta X4. Now am on Alimta maintenance. My Onc wanted me to interview for PDL1 trial and I now have an appointment December 27, 2013.

I believe I will need to test positive for the PDL1 expression. How common is that expression?
Is it something most cancers express?

Thanks for your help on this one,
Vicki

Reply # - December 17, 2013, 06:59 PM

catdander
Posts:

Hi Vicki, I don't have the answer you're looking for yet but here's a some figures from the still pretty small data pool. http://cancergrace.org/lung/2013/10/01/mpdl3280a-esmo/

I'll look around some more. I know it's been stated here before, however the number of people who've been tested are still so small that the suggestion that those with a higher PDL 1 expression do better is still just a possibility. In the blog linked to above Dr. West states, "while these results were called a potential “game changer” in Amsterdam, they are still based on small numbers, and we should be cautious when we know that the definitions of response can be especially challenging with immunotherapy, where new nodules that turn out to not be cancer may appear and you sometimes see what appears to be progression before a response (and these cases are not categorized as a response). If a single additional never-smoker had demonstrated an objective response, the response rate would have been essentially the same between smokers and never-smokers (26% vs. 20%)."

Janine

Reply # - December 17, 2013, 07:11 PM

catdander
Posts:

It looks like the percentages of those with nsclc who express PDL1 (I don't know if I'm saying that right) are somewhere between 45-50%. 45 for those with adeno and 50 for those with squamous. Squamous nsclc is most often found in smokers and ex smokers.

There aren't transcripts or powerpoints for the video but you can find the slide with the figures you're looking for at the beginning of the video.

http://cancergrace.org/lung/2013/09/12/asco-2013-mpdl3280a-nsclc/

All the Very Best of luck,
Janine

Previous PostNext Post