Has PD 1 shown any pos. results for NSCLC Mucinous BAC? - 1264562

I haven't yet heard of any results either way for immune checkpoint inhibitor therapy for patients with mucinous BAC, either in terms of presented/published results or even anecdotal reports. If anyone else has information about this, I'd learn from it too.

-Dr. West

Hi kapleasants,
My wife has mBAC. Has been twice on Carbo-Alimta doublet and the remainder on Alimta maintenance in the last two years and three months. She is eligible to participate in the Roche trial. Has done all the testing in the past week and we should know tomorrow whether she is accepted and if so whether she will get the MPDL3280A or the Taxotere with treatment to start later this week.
I do recall reading about a case about someone at the tail end of a Phase II who had good things to say. He had NSCLC but do not recall readily whether he had mBAC. I will see whether I can find it again and if so will post details.
Will also post the outcome on what will be next for my wife once we have the word.
Best wishes to you.
Dutch46

Hi Kathy,
Thanks for your kind message. Learned this morning that my wife will participate in the clinical trial and has been assigned treatment with Taxotere (docetaxel). We had hoped for the experimental drug but that avenue is closed for now until it has been approved by the FDA. She has the BRAF V600E mutation so we will be looking at back up treatments if she fails to respond to the Taxotere. Have contact with someone with NSCLC, the BRAF mutation, and has been on Zelboraf (mainly used in melanoma where this gene mutation is more common), with good results so far.
We were fortunate that my wife responded so well to Carbo-Alimta, followed by Alimta maintenance, for as long as she did.
We well understand the unnerving unknown. We are now again where we were almost 2-1/2 years ago after she was declared free following here lobectomy. However, the only way to go is forward. There are numerous promising developments and I think they will get better in getting patients quicker on promising drugs.
As to this particular clinical trial we were encouraged by early data showing response from 25 % for patients with no expression of the PD-L1 up to 60-65 % for patients with a high expression, hence our wish to get the experimental drug. Had we not done the clinical trial the Taxotere would have been the second line anyhow.
Bear in mind that while the trial is for one year, you are not stuck in it. You can withdraw from it at any time.
Here is a link to the poster as was shown at the most recent ASCO conference.
www.mpdl3280a.com/ASCO2014/ASCO2014-Poster-Rizvi.pdf
Wish you well and the strength to make difficult decisions.
Best wishes to you.
Dutch

Hi Kathy,
Well, as you said, we have to work with the cards we have been dealt. My wife is a real trooper and that is half the job.
I would think that in the trial they will try to have an equally representative distribution of patients' profiles on both the experimental and standard chemo side for a proper comparison of the efficacy of the experimental drug against the standard chemo. If Phase I or Phase II has shown that MPDL3280A is only effective on solid tumors I doubt they would have included mBAC in the Phase III trial, but I may be wrong.
We hope that the Taxotere does work but there are a different set of side effects compared to platinum based chemos, specifically, osteonecrosis, bone disorder and related bone issues. This could become a concern.
Interesting what you said about how well the Alimta with the Avastin worked for you for two years. Will raise that question with our onc.
When there are no clear solutions to the problems at hand one strives for making the best informed decision possible and go from there. In a good case scenario we get another long period of stability and enough time to catch the next promising development. If not, we just have to go to the next best thing. Unfortunately, most oncs can't agree on what that should be and that is where you and my wife and I and others in similar situations will have to make that call.
Will update you on her response to the treatment and any changes we may (have to) contemplate down the long and winding road.
Wish you well and let me know when things change for you and if you enroll in the same trial which drug you will be getting.
Best wishes,
Dutch

Hi Kathy,
The person I had referred to yesterday, he has squamous cell LC. He is in Phase II trial. Has been stable since and with virtually no issue with side effects.
Dutch

I think the story so far has been that genetically complex, carcinogen-induced tumors with more mutational load tend to respond better to checkpoint inhibitors like aPD-L1. That may be because these types of tumors have more abnormal foreign antigens for dendritic cells to process and present to T-cells (they leave a bigger footprint for your immune system 'detectives' to pick up on).
You can contrast that type of tumor to the lazy, low-grade bronchoalveolar in-situ type of neoplastic process that is sometimes seen in never-smokers. On a purely anecodotal basis, I haven't heard of many dramatic success stories with checkpoint inhibitors for that type of process, especially for the chemo-naive setting. Nonetheless, I'm sure there have been a few.

Dr. Creelan,
What then might be the rationale to include mBAC patients in this trial? Each group should have an about even distribution of expression, subtype of LCs, and so on. If there is a real or perceived low expectation for low grade cancers like mBAC does that not take away from the objective to determine the optimal efficacy of MPDl3280A in itself and in comparison with Docetaxel?
Also, economics would dictate to structure the trial in such a way that the best possible outcome can be achieved. Now, if low grade cancers are only assigned Docetaxel and not the experimental drug, based on the earlier mentioned expectation the outcome will then be skewed towards the experimental drug based on a flawed distribution, and one would think that the FDA would not fall for that, but then the financial stakes are extremely high.
Earlier MPDL3280A trials indicated that even with little or no expression there was a 25% response rate, so can I assume then that mBAC would likely fall into that category?
Being a layman excuse my use of terminology but trust you will understand what I am saying.
Sincerely,
Dutch

At this point, this discussion about odds of response is essentially just speculation. Since we treat mBAC similiar to other types of non-small cell lung cancers, it is reasonable to include all non-squamous histologies as a single category. Just like cancer itself, the immune system is very complicated and sometimes almost capricious in its behavior. Clues are emerging about drug response, but it may be years before anyone figures this all out.