@bionicbeckyrocks can you copy and paste this into a new discussion where it will be seen better?

@bionicbeckyrocks welcome to Mayo Connect! sorry to hear you're having recurrence and that Tagrisso has been tough on you. is your care team helping you manage the side effects? I would hope they could help you not be bedridden and nauseated. my mom had lymphoma, but acupuncture and cannabis helped her nausea while she was undergoing chemo.

Welcome @bionicbeckyrocks, I love your screen name, and it instills a sense that you want to continue fighting this disease. These targeted therapies can be hard for your body to process. Hopefully they will find one that works for you without all of these side effects. I can't image having to live in a constant state of not feeling well. To be clear, I'm a patient like you (ALK positive), not a clinician. Some oncologists will recommend a dose-reduction when side effects are impacting you to this extent. During your break from Tagrisso, did your issues resolve?
The Rybrevant has been approved for EGFR non-small cell lung cancer just in the past two years, and it was developed to cover the exon 20 insertion mutations. After searching the group posts, I'm not finding other mentions of it, but that doesn't mean that someone won't chime in. Is the rare part of your EGFR exon 20 insertion?
(https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-amivantamab-vmjw-egfr-exon-20-insertion-mutated-non-small-cell-lung-cancer-indications)
Some of the chemo regimens that are given in conjunction with a targeted therapy may be tolerated better than some stronger chemos. Have you had appointments that outlined what to expect with the new treatments? Are you being treated at a cancer center that you trust? Do they have experience in treating other EGFR patients?

@bionicbeckyrocks
I took Tagrisso followed by the chem doublet (carboplatin and pemetrexed) and Rybrevant (amivantamab). The problem is that everyone’s reaction to treatment is specific to that person but here goes:

1. I took Tagrisso for 9 months, the first 6 weeks at 80 mg, then dropping to 40 mg because of side effects. Side effects were tolerable on the reduced dose.
Tagrisso did NOT work for me. The first 3-month scan after starting Tagrisso showed progression (ground glass nodules turned solid) and the 9-month scan (still on Tagrisso) showed metastasis to the mediastinal area between the lungs (the first time I had progression outside of the lungs themselves, although still within the chest cavity). I stopped Tagrisso.

2. I started the chemo doublet (carboplatin and pemetrexed) with Rybrevant (amivantamab). I had significant side effects (to me; my doctor kept telling me I looked good) but managed the first four weekly treatments and another treatment 3 weeks after the weekly treatments ended. I learned that my oncologist had been giving me the Rybrevant at a dose intended for patients who weighed 175 pounds or more. I weighed 124 pounds when I started the chemo/Rybrevant treatment but dropped to 103 pounds. The doctor agreed to stop Rybrevant but wanted me to continue the chemo doublet.

3. Before I could decide whether to do additional chemotherapy as recommended, I developed sepsis/septicemia. I spent three weeks in the hospital, followed by twice daily self-administered infusions of antibiotics at home for a month. It took almost six months before I felt like myself.

4. The kicker: the treatment worked. The growth in the mediastinal area resolved and nodules in the lungs either shrunk or resolved. I did not start maintenance treatments (usually pemetrexed and continued amivantamab/Rybrevant, possibly Lazertinib, every three weeks). I was still recovering from the sepsis and I was extremely reluctant to return to any treatment.

5. Six months later, I again have progression, into the mediastinal area again as well as increased size of the growths in the lungs. I am in the same spot you are: do I do treatment? If I do treatment, which treatment?

Datroway (datopotamab deruxtecan), also known as Dato-DXd, has been recommended as my next treatment. Recently, it seems that it is being recommended as the next treatment after failure on Tagrisso (https://egfrchannel.onclive.com/nccn-releases-nsclc-guideline-update-dato-dxd-designated-as-a-preferred-second-line-regimen-in-egfr-mutated-disease/ ), so it is a recommended option to Amnivantamab (Rybrevant). Datopotamab and Amnivantamab have different primary side effects. (Although Datopotamab lists hair loss as a side effect, I have read that it is more thinning than total loss. I did not have hair loss on amnivantamab.)

These decisions are very unsettling. I am not sure my experience can help but I’m too close a match to your situation not to respond, although I do not have metases to the bones, which would add to the urgency of your decision. I might even have made things worse by introducing another option to Rybrevant.