I joined GRACE as a caregiver for my husband who had a Pancoast tumor, NSCLC stage III in 2009. He had curative chemo/rads then it was believed he had a recurrence in the spine/oligometastasis that was radiated. He's 10 years out from treatment.

I am here on behalf of my mom, an otherwise-healthy, never-smoker Chinese woman from Hong Kong who now lives in California. She was diagnosed at age 63 in Nov. 2018 with stage IV non-small cell lung cancer/adenocarcinoma, with a moderate-sized right pleural effusion and four masses in her right middle lobe/upper lobe/lower lung. Brain MRI and PET CT negative for metastases. NeoTYPE analysis of right pleural fluid showed the uncommon EGFR exon 18 and exon 20 compound mutation, G719S and S768I, in addition to SMAD4 (V354G). Guardant360 analysis of her blood showed EGFR G719S, EGFR S768I, and CTNNB1 S33F. She has been on Afatinib (Gilotrif) 30 mg daily starting Dec. 2018.

Because my mom's mutation is uncommon and it seems that not as much info is known about other medications besides Afatinib that may work well, I am eager to connect with other caregivers or patients who have the same compound mutation with the hope of sharing info/support as we continue to provide care. She has been on afatinib as first-line treatment for 4 years since December 2018. Other than a small nodule that popped up in her right lower lobe two years ago that was radiated, she has been stable and feeling great. However, her CEA has been rising significantly (from 27 in May 2021 to 461 in 11/2022) and finally, a PET-CT in 11/2022 showed that her right hilar lymph node is lighting up with SUV Max of 8.6. There is also mild hypermetabolism in her sternum (SUV Max 3.5) and right posterior ninth rib (SUV Max 4). Her brain MRI on 10/2022 was normal. Her PET-CT on 12/2021 was already showing mild hypermetabolism and an increase in size in two sclerotic lesions in her sternum, and I had been asking about radiating them last year - however, her oncologists said that it was not concerning at the time (one of them thought the SUV was insignificant, the other said if they were bone mets, they should not be radiated unless they are causing pain). I now wonder if we had radiated the sternal lesions last year, would it have prevented the extent of progression we are seeing now? Or was her sternum just the first place that the resistant cancer showed up, and progression was bound to show up elsewhere? She is planning to get a bronchoscopy/biopsy of her lymph node in 12/2022 and we'll see what mutations show up. Her second opinion oncologist at UC Davis said it would be good news if we see T790M, but based on the little research on patients with her rare compound mutation (exon 18 G719S + exon 20 S768I) + T790M, it seems that Tagrisso can sometimes work and sometimes it doesn't work at all. He said there are many things we can do and her progression seems to be mild right now so she can keep taking afatinib while we are waiting for her biopsy, but we need to be considering a change in systemic treatment. It's a shame since afatinib seems to be keeping the original nodules in her right lung stable. I was hoping that she could simply have her new spots radiated and continue staying on afatinib successfully. Her Foundation One blood biopsy showed EGFR S768I, SUFU L140fs*1, DNMT3A R484fs*8, bTMB 0 Muts/Mb. Her oncologist said he doesn't think the new findings of SUFU L140fs*1 and DNMT3A are driving her cancer progression. We were advised by integrative oncologist Dr. Michael Castro (Beverly Hills Cancer Center) last year to order Tempus xE for whole exome sequencing, then OmiCure for gene expression analysis and biosimulation via Cellworks using in silico computation biological modeling to create an in silico avatar of the cancer (he said this would "permit simulation of drug responsiveness with her unique disease network to stratify the most and least important abnormalities"). I'll need to see if her primary thoracic oncologist at UCSF will be on board - I'm guessing he will think it's not necessary to order whole exome sequencing but that it won't hurt if we are willing to pay for it. Issue is that the turnaround time for Tempus xE whole exome sequencing is 4-5 weeks (at least 2 weeks longer than a regular tissue biopsy) so hopefully that delay won't make a difference in her care?

Thanks a lot for reading - we would greatly appreciate any thoughts or advice from this group.