merck approval for keytruda - 1266700

Hi phillydaughter,

Keytruda (pembrolizumab) is now an approved treatment for melanoma, but as long as it is an approved drug for something, a doctor may prescribe it off-label. For the most part, off-label use is not covered by insurance, including Medicare, although with insurance companies it is sometimes possible to provide enough evidence to convince them that its use in your situation is not investigational and it should be covered. My wife's oncologist successfully did this with Abraxane before it was approved for NSCLC. With Medicare, the drug must be compendia listed before its use will be reimbursed.

Recently, Dr. West had this to say about the availability of these immunotherapies (including Keytruda):

"I don’t think any of these options will have any meaningful chance of being compendia listed before the data on nivolumab’s large phase III trials in the second line setting are presented. After that, if positive (and everyone is hopeful that will be the case), I suspect it will only be a matter of months before the FDA approves it. Between the presentation of any positive data and an official FDA approval, there may well be a short interval of availability on a compassionate use basis, and I don’t know if there will be any real interval between compendia listing and FDA approval. Meanwhile, the other immune checkpoint inhibitors as well as nivolumab will also be the subject of a wide array of clinical trials that will serve as another way to have patients receive one of these agents." - http://cancergrace.org/topic/immunotherapy-patient-forum#post-1266550

As far as getting excited, this is one more step on the road to these drugs becoming widely available, and so it's a good reason for at least increased optimism.

JimC
Forum moderator

It means that it could be approved based on significant data that isn't necessarily a significant improvement in survival. It won't lead to it being available for lung cancer patients any time soon unless they are willing to pay about $150K/year for it.

-Dr. West

I've read there seems to be a strong correlation/association with KRAS/PD-1 expression. This could be great news (one day) for those KRAS+ ?

With regard to KRAS and PD-1, Dr. West has stated:

"I don’t think there has ever been anything presented or published about benefit of anti-PD1 being more or less in patients with KRAS mutations, EGFR mutation, or any other molecular marker. To my knowledge, there is no reason to think that someone with a KRAS mutation should be less likely to benefit than anyone else. It should not be an exclusion criterion.

The main class of targeted therapies that are being studied as being focused largely on patients with a KRAS mutation are MEK inhibitors like selumetinib, which is the subject of a phase III trial just being activated globally, giving Taxotere (docetaxel) with or without selumetinib as second line therapy to patients with a KRAS mutation." - http://cancergrace.org/topic/lung-adenocarcinoma-with-k-ras#post-1258662

It may take some time, but encouraging research into MEK inhibitors continues, as Dr. West describes here. And Dr. Leighl presented more information here.

JimC
Forum moderator

There hasn't been any meaningful association of KRAS mutation status and PD-L1 expression. I've been at lung cancer meetings and immunotherapy meetings for the past week, and this has never come up as an association. Right now, there's a general sense that PD-L1 expression is not a very clear predictor of benefit with immune checkpoint inhibitors as it is, and there's definitely no sense that KRAS mutation status serves as a useful proxy or strong correlate.

Sorry...

-Dr. West

Thanks Jim/Jack.

This is the (small) paper I was refering to.

http://journals.lww.com/jto/Fulltext/2014/04001/Abstracts.6.aspx

ttfn

The link goes to a long list of abstracts. What is the number/code of the abstract in question?

Dr. West,

It's number 38O, and included 29 KRAS-positive patients. The study showed a correlation between that mutation and high PD-1 expression.

JimC
Forum moderator

No, this is a single report in a sea of studies with different results all over the map. Even PD-L1 expression itself is of very questionable value as a predictive marker for immune checkpoint inhibitors, so something that seems to correlate in one report but has never been reported as a correlation elsewhere, with a marker that itself is of dubious value, is really not a result that will have any impact on cancer treatment in the real world.

Sorry.

-Dr. West

Sorry Jim/Jack - this is the direct link to abstract:

https://www.iaslc.org/articles/elcc-2014-pd-l1-and-pd-1-expression-coho…

Obviously a small study... And just to be clear it seems to show PD-1 correlated with KRAS, and PD-L1 with EGFR.

Yes, thank you for the correction. I've edited my earlier post.

JimC
Forum moderator