Osimertinib (Tagrisso) with dexamethasone - 1294717

5 posts / 0 new
Last post
daxys
Osimertinib (Tagrisso) with dexamethasone - 1294717

Is anyone on Tagrisso (osimertinib) taking or took dexamethasone? I want to start my mum on osimertinib, but she is taking dexamethasone for brain lesion edema. I learned there might be interaction between these two : dexamethasone may reduce the blood levels of osimertinib, which may make the medication less effective in some cases. Does anyone have any experience or recommendations and did you have good response from Tagrisso while on dexamethasone?

onthemark
Hi Daxys,

Hi Daxys,

Welcome to GRACE. It's best to discuss your concerns with your oncologist, but in the meantime if you look at the physician desk reference page on Tagrisso, which exhaustively lists all the drug interactions that are significant enough for doctors to take into account, it doesn't list dexamethasone or decadron.

See: http://www.pdr.net/drug-summary/Tagrisso-osimertinib-3828

Drugs can have weak interactions but not enough to change how medications are prescribed or patients monitored.

Since Tagrisso crosses the blood brain barrier, hopefully your Mum has a good response and it will shrink the mets in the brain so your Mum may not need to stay on Dexamethasone. Sometimes Tagrisso is prescribed at double dose (160 mg rather than 80 mg) for patients with brain mets.

JimC
Hi daxys,

Hi daxys,

I'll add my welcome to GRACE, as well as a bit more information in addition to what onthemark has already provided.

The interaction between osimertinib and dexamethasone is one which is predicted because dex is a weak CYP3A inducer. As onthemark points out, trial experience hasn't revealed enough of an interaction to warrant including dex interaction in the prescribing information for Tagrisso. In a study of such possible interactions, it was concluded:

Based on observed clinical data and PBPK simulations, the recommended dose of osimertinib when dosed with strong CYP3A inducers is 160 mg once daily. PBPK modeling suggested no dose adjustment with moderate and weak CYP3A inducers. - https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/psp4.12289

Although we wouldn't expect an interaction of any significance, at worst the dosage of either Tagrisso or dexamethasone would simply need to be adjusted.

Good luck to your mum with Tagrisso!

JimC
Forum moderator

<p>I began visiting GRACE in July, 2008 when my wife Liz was diagnosed with lung cancer, and became a forum moderator in January, 2010. My beloved wife of 30 years passed away Nov. 4, 2011 after battling stage IV lung cancer for 3 years and 4 months</p>

daxys
Thanks to both of you for

Thanks to both of you for your fast replies! I did some research yesterday and I guess I got basically the same information. Also I found a study which deals with various doses of osimertinib and confirms that there is no difference in efficacy :
http://oncologypro.esmo.org/Meeting-Resources/ESMO-Asia-2017-Congress/Th...

So I guess even if there were some little interaction it should not change the effect of osimertinib. I would like that osimertinib does its best for my mum and still I would like to hear from people who took it along with dexamethasone.

onthemark
A Dec 2017 paper:

A Dec 2017 paper:

"Emerging biomarkers for the combination of radiotherapy (RT) and immune
checkpoint blockers (ICB)"

links to Jim's and Dr. West's remarks about biomarkers and summarizes the current state of knowledge.

RT increases the antigenicity of malignant cells by promoting the upregulation of MHC class I molecules on the cell surface [10,11], by favoring the expression of tumor-associated antigens [12], and (at
least potentially) by enhancing genetic instability or reactivating endogenous retroviruses [13,14]. Moreover, RT boosts the adjuvanticity of cancer cells by at least two mechanisms...

"The potential predictive value of the biomarkers discussed above needs to be studied in patients receiving RT plus ICBs. Indeed, some of the biomarkers that are associated with improved clinical responses to RT or ICB-based immunotherapy may have limited predictive value in the context of combinatorial regimens. As an example, while high PDL1 expression levels are robustly associated with the response of melanoma and NSCLC patients to nivolumab or pembrolizumab (see above), a benefit on progression-free survival was observed irrespective of baseline PD-L1 expression in NSCLC patients treated with chemoradiation followed by durvalumab versus placebo [130]. This result is consistent with the hypothesis that RT can induce PD-L1 expression in the tumor microenvironment, as demonstrated in preclinical settings
[131]...
Here, we will focus our discussion on mechanism-based biomarkers that are emerging as candidates
to specifically predict the response to RT plus ICBs (not necessarily to either of these treatments administered alone).