Tagrisso 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

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

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

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