Any ‘plan B’ will depend on the way in which a cancer becomes resistant to Tagrisso (osimertinib). The following provides a general overview of “Trends in Treatment of EGFR+ NSCLC after Progression Following Tagrisso Treatment”:
https://go2.org/blog/trends-in-treatment-of-egfr-nsclc-after-progression-following-tagrisso-treatment/#:~:text=Since%20IMpower150%2C%20some%20doctors%20may,have%20progression%20after%20receiving%20Tagrisso
For a more detailed understanding, an organization called EGFR Resisters has an excellent webinair series on the different ways in which EGFR-positive cancer becomes resistant to targeted treatment. The various means of resistance can be divided into three categories and there is a video on each of those categories; see the following for links to the videos: https://egfrcancer.org/ask-the-egfr-experts/#videos Each video also provides an overview (following an introduction: be patient!) and each overview is helpful even though they are slightly different (it helps to hear about this more than once!).

The videos are around 45 minutes each but I certainly found them worth my time. There is also a link to fact sheets. I recommend signing up for the newsletter from EGFR resisters, which will let you know about advances and new education material; you’ll get the chance to sign up from their home page https://egfrcancer.org

I hope this helps. At this point, it really makes sense to achieve a general understanding because you won’t know what kind of treatment is next until you know what kind of resistance is encountered. I hope that Tagrisso will remain effective for your wife for a very long time, at which point there will undoubtedly be many new possibilities for treating resistance.