When to begin exploring immunotherpy - 1270550

zhengchenji18
Posts:26

Hi,
My dad was diagnosed with stage IV NSCLC with bone metastasis about Sept 2013.
He started taking Irressa in Nov 2013.
In Feb 2015, he started progressing on Iressa and entered the AZD9291 trial.
Currently, the 2nd EGFR inhibitor AZD9291 is working and he is stable.

Eventually, however, he will progress on AZD9291 and we will have to explore options.

From my research, the leading immunotherpy drugs in clinical trial are two below.
Nivolumab CheckMate 012
MEDI4736

Question:
1.Those are the two available in Toronto, is there any other promising drugs in US?
I believe Nivolumab and MEDI4736 are both anti PD-L1, is there any other types?

2.When is the good time to explore immunotherpy?
The standard care after progression on AZD9291 is chemo with either cis or carbo.
Should we explore immunotherpy before or after chemo.

3.Is there any other alternatives besides chemo?
Maybe a another EGFR inhibitor?(just a wild guess)

Thanks!
Fischer

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Reply # - July 22, 2015, 09:05 AM

JimC
Posts: 2753

Hi Fischer,

It's good to hear that AZD9291 has been effective, and I hope it remains so for quite a long time, perhaps long enough to make any of the information currently available obsolete.

Although the standard of care after progression is currently chemotherapy with established agents, that is mainly so because these are drugs that are already approved and have a proven track record, rather than treatments (such as immunotherapies) which are still investigational or newly approved. You can choose either order of treatment, although in some cases trials have entry limits on how many agents have been previously used. That would suggest moving to immunotherapy first. On the other hand, since it usually takes some time before immunotherapies begin to show efficacy, if progression is rapid enough established chemo agents may be preferred since they can show benefit after just a couple of treatment cycles.

There are other agents, but there really isn't a great deal of evidence supporting the use of a third EGFR TKI. You can search GRACE for "third generation EGFR inhibitor" and get a number of results, including these:

http://cancergrace.org/lung/2014/09/30/acquired-resistance-impress-esmo/
http://cancergrace.org/lung/2014/05/12/iaslc_wakelee_egfr_drug_co-1686/

Again, I hope that you do not face this decision any time soon.

JimC
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Reply # - July 22, 2015, 11:36 AM

biggerten
Posts: 83

Both are PD pathway agents, MEDI4736 acts against PD-L1, Nivolumab (Opdivo) against PD-1. MEDI4736 is similar to MPDL3280A (atezolizumab), and Nivolumab is similar to pembrolizumab (Keytruda).

Reply # - November 15, 2015, 04:40 PM

zhengchenji18
Posts: 26

https://www.youtube.com/watch?v=vZbDi8Ukdy8

The video above commented on the fact that immunotheorpy is less success for patients with EGFR mutation.
I just want to clarify what they are saying.

As mentioned earlier, my dad is currently take the AZD9291 drug which is the third generation EGFR inhibitor.
After AZD9291 become ineffective, the tumor is likely becoming a wild type of EGFR mutation.
In this case, would immunotherapy works?
Is the video suggesting all types of EGFR mutation for a specific type that can be treated with 1st/3rd generation EGFR inhibitor?

I am trying to see if my dad would be able to take immunotherapy in the future.
Currently, he is not allowed as he have EGFR mutation.

Thanks,
Fischer

Reply # - November 15, 2015, 05:56 PM

carrigallen
Posts: 194

As mentioned above, my enthusiasm is rather low for giving PD1 or PD-L1 inhibitors as single drugs to never-smokers with activating EGFR mutation. The chances of durable response seem to be rather rare in this setting. Why? It appears these EGFR mutant tumors often aren't genetically bizarre enough to be rejected as non-self by our T-cells.

There have been a few good responses with EGFRm tumors seen with CTLA4 plus PD(L)1 combinations, and there are certainly several trials looking at EGFR inhibitors plus PD(L)1 inhibitors. So I would advocate for a clinical trial in this setting.

If a trial is not an option, then standard traditional chemotherapy is still an attractive option for EGFRm patients. Drugs like Carboplatin with Alimta or Gemzar do not cause noticeable hair loss for most patients, and are often effective and well-tolerated.

Reply # - November 15, 2015, 07:19 PM

zhengchenji18
Posts: 26

Thanks for your fast reply Dr Ben Creelan.
It really clarify the issue for me.

You mentioned that there are clinical trails for
1. CTLA4 + PDL1
2. EGFR inihibitors + PDL1

If it is not too difficult, could you provide the one trail number for each possibility?
Or if there is a centralized website I can just search myself.

Many thanks!
Fischer

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