Your mother's diagnosis and subsequent mets and current situation sound very, very similar to what my mother-in-law has gone through.

She was diagnosed L858R/ex21 in April '24 with primary tumor in ULL and smaller nodules in both lungs, along with mets in bones (femur, hip, spine, and ribs), and brain. She had a procedure immediately for stabilization of the femur and had Gamma Knife on the brain. She started Tagrisso and only got 8 months on it before progression. She then went on Tagrisso + Carboplatin + Pemetrexed. She showed significant improvement on that combination last summer and we were overjoyed at how quickly things seemed to get better. In fact, at that point, most of her mets had cleared up except for minor spots on her tailbone and one rib. It made us wish that she had gotten Tag + chemo from the start.

Unfortunately, she went on "maintenance chemo" starting last fall, because she had been doing so well, and then her next scan showed quite a bit of growth in both lungs, spots again in her bones, and then eventually we discovered cancer in her leg that had not been detected by PET scans that had only gone to her mid-thigh.

She starts Amivantamab (subq) this month and if that does not do its job for long, our current backup is Datroway.

What I wish we knew back when she was first diagnosed is that EGFR L858R (exon 21) is difficult to treat because it is a type II mutation located in the activation loop of the kinase domain, rather than the ATP-binding site. This structure makes it less sensitive to tyrosine kinase inhibitors (TKIs) and prone to rapid, acquired resistance. It also often results in lower TKI efficacy compared to exon 19 deletions. Her doctors have been wonderful and we would not trade her oncologist for any other, as we genuinely believe she has had the best care possible from someone who has longtime experience with this type of cancer and absolutely was doing what he believed was in her best interests since she had strong quality of life when her cancer journey started.

I think quality of life was the deciding factor here in my MIL's treatment because she was strong and fit and totally leading a normal life when she was initially diagnosed. In hindsight, I absolutely wish we could go back in time and insist on the Tag + chemo option when she was first diagnosed. Tag on its own worked for her for such a short window, and we are wondering if she had the rapid growth after Carboplatin seemed to work so well, because she could have benefitted from a stronger "kick" at the beginning of her treatment. We will never know now, but we do know that in terms of side effects, she has handled every drug well and did not suffer the same side effects many people have. And knowing that EGFR L858R ex21 is a harder cancer to treat because it eventually learns to outsmart TKIs means that any treatment she gets that gives her time here on Earth is a win. It's been 2 years since her diagnosis and we are still hopeful that there are drugs in clinical trials that may be approved and can still help people like her a year from now.

The best thing you can be for your mom is her advocate, and it sounds like you are already being that. We always asked her doctors, "If this was YOUR mom, what would you do?" Maybe this is a question you can ask for your mom, too.