Opdivo, Keytruda and Tecentriq mechanism in PDL1 negative patients

Portal Forums Cancer Treatments / Symptom Management Immune-based Therapy / Vaccines Opdivo, Keytruda and Tecentriq mechanism in PDL1 negative patients

This topic contains 4 replies, has 4 voices, and was last updated by catdander forum moderator catdander forum moderator 1 year ago.

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October 11, 2016 at 9:13 am  #1288895    

fanos

I have read (including the latest on Grace) about the PD1-PDL1 pathway and how these drugs appear to fight the cancer cells. However it is not clear that if the cancer cells do NOT (or minimally) express the PDL1 how the Opdivo (or Tecentriq) can have a better outcome than Keytruda (which requires >50% PDL1 expression on the cancer cells). If the PD1 is blocked but there is no PDL1 on the cancer cells, what then is the mechanism that is blocked. My daughter tested 100% PDL1 negative so I would like to understand why her doctor would put her on Opdivo. Please explain the mechanism that Opdivo would take when the results given-no PDL1. Thank you.

October 11, 2016 at 2:37 pm  #1288898    
catdander forum moderator
catdander forum moderator

Hi fanos,

I’m so sorry about your daughter’s diagnosis Without speaking directly to your daughter’s oncologist you won’t know her/his thought process. It could be that she is otherwise a likely candidate such as has a squamous nsclc or has adeno with a smoking history and or has no known driver mutations. It is possible that the sample tested is thought not to be a good representation of the cancer. Perhaps there are no other treatment options and the onc wants to make sure everything has been tried.

You’re right it’s not as likely a person without an expression of somewhere around 50% PD-L1 will respond well to immunotherapy. There is a PD-1 receptor on immune cells and some cancer cells have a PD-L1 receptor that causes a block between the immune system and the cancer. We are still in the very early stages of understanding. There’s a reason why the immune system isn’t responding so obviously there’s more to it.
This is a link to a good explanation of what we know about immunotherapies mechanism of action, http://cancergrace.org/cancer-treatments/2014/12/11/it_forum_what_immunotherapy_mechanisms_action_pt1/

I’m sorry there are no best answers and I hope your daughter does well for a long time.

Janine

October 11, 2016 at 2:58 pm  #1288899    
JimC Forum Moderator
JimC Forum Moderator

Hi fanos,

In addition to the great information already provided by Janine, while she was writing I was reviewing another post by Dr. West dealing with the value of PD-L1 testing and the differences in response (and eventual approval) of Keytruda and Opdivo. He points out that although Opdivo seems to have some efficacy for PD-L1-negative patients and is approved for use by such patients (while Keytruda is not), that’s due more to the differences in the clinical trials that led to each of these drugs’ approvals than a difference in the mechanism of action of these agents. Also note that in the addendum to his post, Dr. West softens his stance on whether second-line Taxotere (docetaxel) is clearly superior to Opdivo in that setting.

He also states that he feels all patients should get an opportunity at treatment with an immunotherapy agent at some point.

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

October 21, 2016 at 7:09 am  #1288978    

neeneebeans

I failed to benefit from Optivo and have tested PD-L1 neg., does this indicate that Tecentriq would not be worth trying?

October 21, 2016 at 12:14 pm  #1288981    
catdander forum moderator
catdander forum moderator

Hi neeneebeans, I love your username.

The quick answer is we don’t know. There is evidence that suggests one works as well as another. Studies of keytruda, opdivo and Tecentriq appear to have similar outcomes among those with and without pd-l1 expression hence the assumption that if one doesn’t work another probably won’t work either.

Tecentriq targets the pd-l1 receptor whereas keytruda and opdivo target the receptor pd-1 (on the receiving end). That seems to suggest that if there are no pd-l1 receptors to target the drug would not work. However pd-l1 was found and measured on both the tumor and the immune cells for the tecentriq study and was found that tecentriq was most effective for those with pd-l1 expression whether on tumor or on immune cells or both.

That leads to a question of whether you were tested for pd-l1 expression on the tumor only or also on immune cells. And would it matter since you didn’t respond to opdivo? The answers are speculation from the little we know. I’d hate to miss out on a possible effective treatment because of assumptions it wouldn’t work.

I don’t know if you are able since you’ve already had opdivo but there are trials testing combos with immunotherapies with other drugs. That may be an option. Even if your not at a research center then your oncologist should be able to point you in the right direction. Or you can seek a 2nd opinion from a specialist at a large teaching/research center.
This is a recent blog post on about tecentriq, http://cancergrace.org/lung/2016/09/01/oakpos/

Let us know what transpires.
Best of luck,
Janine

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