Tagrisso for acquired resistance to Tarceva

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btlaw123
Tagrisso for acquired resistance to Tarceva

My wife has come a long way with Stage IV lung cancer since 2010. She has now developed acquired resistance to Tarceva.

Gene sequence of biopsy from enlarged pre-vascular and supraclavicular lymph nodes revealed mutation remains EGFR L858R in EXON 21 (original mutation from 2011) and negative to T790M. The cancer is also PD-1 and PD-L1 negative.

Current TAGRISSO indication is for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test

Question:

My wife was treated with Cisplatinum/vinorabine before she was put on Tarceva in 2011. Is she considered not qualified for Tagrisso being that its no longer her first line treatment?

She is also having a possible reccurence in her brain with new MRI enhancement detected on the resected right occipital lobe. I understand that Tagrisso has a better effectiveness in passing through the BBB. Is she a candidate for using Tagrisso in additional to conventional chemo? What exactly is "first line treatment" defined as?

Jim C Forum Mod...
Jim C Forum Moderator's picture
Targrisso for acquired resistance to Tarceva

Hi btlaw,

First line treatment is loosely defined as the first systemic treatment a cancer patient receives. But the approval for Tagrisso as first line lung cancer treatment does not preclude its use at any other point. As long as a drug is approved, oncologists are free to be a bit creative and individualize therapy decisions. At times insurance approval can be an obstacle, but doctors can often provide sufficient evidence of efficacy to gain that approval. JimC Forum Moderator

btlaw123
Can Tagrisso be used for patients with no T790M mutation

Thank you Jim for the quick reply. With the recent revision in the indication for Tagrisso, is it true that Tagrisso is not just for patients with T790M mutation + only?

Jim C Forum Mod...
Jim C Forum Moderator's picture
Targrisso for acquired resistance to Tarceva

Hi btlaw, The specific approval for Tagrisso is for either first-line treatment of EGFR positive NSCLC or T790M positive NSCLC after progression on EGFR TKI therapy. See Section 1 of the Tagrisso prescribing information which can be found at: https://www.azpicentral.com/tagrisso/tagrisso.pdf#page=1 But there is evidence that it can be effective after previous TKI therapy without evidence of a T790M mutation: https://www.jto.org/article/S1556-0864(17)32023-3/fulltext (Only the first page is available without cost, but it does contain a summary of the results). As I cautioned above, insurance coverage may be an issue, but if your doctor provides your carrier with evidence such as the cited study, perhaps they will agree to cover it. Jim C Forum Moderator

btlaw123
The Tagrisso prescribing

The Tagrisso prescribing information page is quite confusing. Since my wife was on Tarceva for over 6 years and have now "developed acquired resistance" and even with brain mets returning, just wondering if Tagrisso would work? I read about its known property that it would penetrate the BBB and provide good cancer control in the CNS.

Tarceva being a first generation TKI and Tagrisso also a TKI (although a newer drug), one would say that it may not work. My wife's mutation status remained EGFR L858R on axon 21 without the T790M driver mutation. Since Tarceva is no longer controlling her cancer, (acquired resistance without T790M??) does that automatically disqualified her from using Tagrisso?

btlaw123
Acquired resistance to Tarceva

Does having developed acquired resistance to Tarceva but without the T790M mutation automatically disqualify a person from using Tagrisso?

Jim C Forum Mod...
Jim C Forum Moderator's picture
Tagrisso Prescribing information

Hi btlaw,

Sorry I didn't make this clearer. The prescribing information lists the only two situations in which Tagrisso is specifically approved for NSCLC. One is first-line treatment. The other is a situation in which a patient has progressed on another EGFR TKI, such as Tarceva, and genetic testing shows the presence of a T790M mutation. Your wife's situation does not fall into either category, since as you stated she has developed acquired resistance without a T790M mutation. But once a drug has been approved in one context, it can be prescribed in other situations, and this happens quite frequently with cancer drugs. For example, there are only a handful of chemotherapy drugs which have been specifically approved for second-line treatment of NSCLC, yet oncologists often prescribe other drugs known to be effective as first-line options, with good success. No one can say whether it will work, but the study I cited provides some evidence that it may be effective, although perhaps less effective than it would for a T790M-positive patient. And since Tagrisso has not been specifically approved in your wife's situation, her insurance may balk at covering it. That's where her doctor may help to convince the insurance company to cover it. Jim C Forum Moderator

btlaw123
Jim, Thank you again for the

Jim, Thank you again for the clarification. I am quoting from the US FDA announcement page about Tagrisso: Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI designed to inhibit both EGFR-sensitising and EGFR T790M-resistance mutations, with clinical activity against CNS metastases." The ending phrase "with clinical activity against CNS metastases" is the real music to my ears for my wife's medical situation!

I remember I read somewhere that Tarceva is know as a "reversible" TKI while Tagrisso is now known as irreversible EGFR-TKI. What exactly the difference between "reversible" vs. "irreversible" referring to? Is that something to do with the side effect or something else? Would someone please provide some information?

JanineT Forum M...
Hi btlaw123,

Hi btlaw123,

First let me ask if you got my private message about moving/filing your thread so the formatting worked? 2nd, the reversible vs irreversible tki has to do with the molecular level bonding of an enzyme that I don't fully understand, (the biology is usually something I take at face value). If you have more questions after watching the video our Oncology Pharmacologist would be happy to answer questions you may have.
Here's a link to a short video that explains it. https://www.youtube.com/watch?v=Sl_JDjsssIM

btlaw123
Janine T

Thanks so much for the video link. No I did not receive your private message. Where can I find it please? Did it go to my email address on record on cancergrace?

Jim C Forum Mod...
Jim C Forum Moderator's picture
Viewing messages

Hi btlaw, We need to improve access to this function, but you should be able to find the message by clicking on the menu icon in the upper right hand corner of the screen, then choose Participate. Select Get Involved from the drop down list, and finally My Dashboard. You'll see a button for messages. Whew! Jim C Forum Moderator