Opdivo, Keytruda and Tecentriq mechanism in PDL1 negative patients - 1288895

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_immun…

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

Janine

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

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

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