Article and Video CATEGORIES

Cancer Journey

Search By

Dr. Jack West is a medical oncologist and thoracic oncology specialist who is the Founder and previously served as President & CEO, currently a member of the Board of Directors of the Global Resource for Advancing Cancer Education (GRACE)

 

Anti-PDL1 Immunotherapy MPDL3280A Observed to Be Particularly Active in Smokers with NSCLC
Author
Howard (Jack) West, MD

There are a few interesting new stories coming out of the 2013 European Society for Medical Oncology (ESMO) conference in Amsterdam that's just wrapping up today.  One has been on the  anti-PDL1 immunotherapy MPDL3280A, an agent from Roche that we saw some initial promising data on at ASCO 2013 earlier this year.  Dr. Jean-Charles Soria from the Institute Gustave Roussy in Villejuif, France presented data on this agent in a larger cohort now of 85 patients for safety data and 53 patients for efficacy.

While again confirming the overall efficacy of this agent, with a response rate of 23%, which tended to be long-lasting at greater than 24 weeks, the angle discussed most enthusiastically was the subgroup analysis of smokers vs. non-smokers. This showed that the response rate was 26% (11 of 43) among smokers vs. 10% (1 of 10) among never-smokers, a finding that is especially striking in the face of so many treatment options that are more frequently directed toward never-smokers. The hypothesis is that smokers are exposed to far more antigens and may have a more immunoreactive form of lung cancer.

Another interesting finding in the trial is that those patients whose tumors expressed higher protein levels of the PD-L1 target had a higher response rate, which was 83% in the minority with 3+ PD-L1 expression and 46% in those with 2+ or 3+ protein expression.

To me, these results again confirm the provocative findings we've seen with "immune checkpoint inhibitors" like nivolumab, an immunotherapy directed against PD-1. It may well be that this tendency toward greater responsiveness in smokers is shared among most or all of these immunotherapies.  But it's also worth bearing in mind that, 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%).   

We need to see this and other immunotherapy agents tested in larger numbers, as is starting to be done on a larger scale.  The early findings are very promising, and I'm very hopeful that MPDL3280A and other agents in this class are active, but it's also worth bearing in mind that Taxotere (docetaxel), an agent we consider pretty mundane now, had a response rate of 25% in phase II testing but turned out to be more like 5-10% in larger studies.  

Next Previous link

Previous PostNext Post

Related Content

Image
Patient Education Ambassadors 2023-24
Video
  Dr. Gladys Rodriguez and Hannah Manella, RD, discuss addressing nutritional concerns of patients who are undergoing cancer care.  
Image
Head And Neck Cancer Program
Video
Drs. Shetal Patel, Siddharth Sheth, and Jared Weiss discuss the most recent advances in head and neck cancer treatment, including curable and incurable head and neck cancers, thyroid cancers, and HPV positive and negative cancers.  

Forum Discussions

Canyil, I'm sorry your father and you are going through this. While we can't give urgent help we are her to help offer info and resources to help make the best...

Hello and welcome to Grace.  I'm sorry you're going through this worry.  It is normal to watch a small very slow-growing solid nodule with once-a-year CT scans.  Anything less than a...

Thanks you very much. So in summary the course of action taken suggested by lung specalist (re scan in 12 months) seems appropriate? And a PET at this stage is probably...

I can't say what is appropriate for you that's only something your professionals with all your information can do.  However, when someone has a solid nodule less than a cm that...

A doctor wouldn't nor shouldn't suspect a pancoast tumor with the info you've given.  It's like being in Colorado and hearing hoof beats and assuming it is zebras and not horses. ...

Hello and welcome to Grace.  I'm sorry you're worrying about this but it probably isn't cancer. 

 

From Adenocarcinoma of the lung: from BAC to the future, "GGNs with diameter...

Recent Comments

JOIN THE CONVERSATION
Canyil, I'm sorry your…
By JanineT GRACE … on
I can't say what is…
By JanineT GRACE … on
Thanks you very much. So in…
By razp on
A doctor wouldn't nor…
By JanineT GRACE … on