Durvalumab not working, based on Guardant 360 Tumor Response Map...

[yenlilly]

Hello All, 

I've been a frequent reader/follower of this discussion forum, albeit never poster (until now), but just want to let everyone know I'm very appreciative of all the technical advice and positive supportive messages that are shared on a daily basis here. I've finally decided to jump in and share my story:

After ~5 months of primary care and pulmonologist appointments/scans/incorrect diagnoses of pneumonia, my never smoker 64 year old mother was diagnosed with Stage 3 Squamous Cell lung cancer in OCT 2021. The tumor biopsy revealed a CDKN2A Deletion mutation, with a high PD-L1 of 90%; and low Tumor Mutation Burden. Once the doc confirmed the best past forward, in DEC 2021, we commenced the chemoradiation sequence of 7 weeks of daily radiation + weekly low dosage chemo treatments of Carbotaxol. 

In FEB 2022, 16 days after the last radiation dose was administered, we immediately began her monthly immunotherapy regimen of Durvalumab (Imfinzi). We did a CT scan at that point that revealed a marked improvement from the PET/CT that was conducted in SEP 2021. The onc also ordered a Guardant 360 test contemporaneously, and we received a baseline tumor response map that indicated she still had relatively low levels 4 separate biomarkers present.

These past 5 months have been (fortunately) mainly uneventful, with the only symptoms presenting being coughing and shortness of breath, likely attributed to a mild to moderate case of pneumonitis from either the chemoradiation of Durvalumab treatment. During this period, I was feverishly researching stats on my mothers case; stats on Durva, and became more and more hopeful that she was going to have a very positive response from the treatment, especially due to her high 90% PD-L1 expression. 

Last month, the onc ordered the another CT scan, which came back very positive, as interpreted by the onc - he said they did not see any additional growth and there was no mention of any masses present - merely increasing consolidative opacity in the perihilar with air bronchograms and moderate pleural effusion, which we assume can be chalked up to the pneumonitis. But the doc's consensus was that this was something to celebrate, as it appears the treatments are working based on the scans alone. To be sure though, he ordered another Guardant 360 test to confirm that, on a molecular level, the treatment is directionally working as intended (ie. we would expect the percentages of each biomarker present in the last test to be trending downwards as the treatment progresses). 

We have not yet had the appointment with the doc to discuss the results of this second Guardant 360 test (will be next week), however, I was able to log on and retrieve the reports on my own and was devastated to see that the biomarker percentages have increased substantially from the FEB 2022 baseline test (see image attached). This directional change would seem to indicate that the Durvalumab treatment is not working for her in the 5 months since she began. My question is, can anyone who has done this test please confirm that that is the accurate interpretation of the results? 

I have not yet discussed with my mom as I do not know what to even tell her. She has been very pragmatic through this whole ordeal, and only just after the last doctor's appointment with the positive CT scan, did she begin to have hope and talk about travel plans for next year, and potentially beyond. This is truly even more devastating to me than the initial diagnosis, as I had such high hopes for this treatment - I was sure that she was going to beat it and be one of the lucky survivors that would last beyond the 5 year mark. Next question here is, what are the next steps for a Stage 3 Squamous Cell (she has not been restaged since initial) chemoradiation patient who, currently only based on the Guardant 360 testing as her tumors have not reappeared yet via scans, does not appear to be responding to Durva? 

Apologies for the long long post here 😌 Appreciate any feedback that I can solicit, and appreciate you all!

Regards,

Lilly

[Tom Galli]

Lilly,

I'm no expert in Guardant testing but have noted inaccuracies in my conversations with survivors on this forum and in other LUNGevity communities. I, therefore, would put your worry on hold until administration of a CT scan or better yet, a PET scan to assess treatment progress.

We have a pretty comprehensive discussion of Durvalumab or Durva as we call it here. It is more than 4 years of history from those who are or have taken this immunotherapy drug and you'll note an overall good survival record.

The best next steps are a CT or PET scan to assess tumor changes.

Stay the course.

Tom

[catlady91]

Hi there Lilly,

I would wait until you speak to your oncologist especially as a lot of reports use medical jargon that non-medical professionals don't understand. Many times I've read my mum's reports and have gotten into a panic. One doctor even put that my mum had metastatic cancer (it was confirmed by the oncologist that it was a mistake on the letter and my and that my mum is indeed stage 3 not stage 4). I read my mum's other medical letters and would research the things that I didn't understand only to get more het up, confused and panicked. 

Don't too much into read into the results. Unless you are a medical professional skilled in that area, you won't know what these results mean. Only your oncologist can interpret these results. 

Also with immunotherapy, there is something called pseudo progression. My mum was told that the cancer "returned" after around 5 or 6 months starting durvalumab but they mistook the inflammation for cancer on the PET scan. The CT scan showed nothing in my mum's lungs and further testing concluded that there was inflammation not cancer. 

Try not to worry and get too worked up. I know it's easier said than done. I've had my fair share of panic and fear reading medical letters. They really don't make these letters and results easy for a lay person to interpret. I would speak to your oncologist or a medical professional.

Monica x

 

[Jeanne Gu]

Hi, Lilly,

After reading through your long email, I found my situation is very close to your Mom's. I am currently under the the treatment of Durvalumab after the CRT. The first CT scan result shows the improvement of the tumor. I do not know about the Guardant360 test until I read your postings. I do not have the answers to your questions, however, agree with other subsequent postings' opinion: let the oncologists/medical professionals interpret the results.

Thank you again for your posting. I will ask my oncologist regarding the Guardant360 test, it is always my concern how to measure the progress of the immunotherapy. Also please relay my message to your mom: I am also a non-smoker with the Squamous stage 3C cancer patient, started the CRT in January 2022, started the Durvalumab therapy in March. I am pretty recovered from the CRT, no severe side effects from the immunotherapy. I am back to work full time now and doing jogging/fitness everyday. Life is going on, keeping the healthy lifestyle, that is all we can do. Let's trust our doctors and our body recovery ability. Even if the cancer goes back/gets worse someday, we can deal with that when it happens.

Best wishes for all,

Jeanne

[catlady91]

I also thought I'd add that's there's no clear test to see whether immunotherapy is working or not other than the cancer getting worse (excluding pseudo progression). Immunotherapy is a fairly new thing and unlike chemo and radiation it can take some time to see if it's working like it did with my mum. 

[yenlilly]

Thank you all so much for your advice and comments - our appointment is this afternoon so hoping that I am completely misinterpreting the results on my own. Agreed that I really should leave this to the professionals, but as you all understand, the anxiety between appointments is debilitating, especially when I have requested early access to these reports. 

The blood test I believe we are utilizing is the Guardant360 Response test (press release here from last year: https://investors.guardanthealth.com/press-releases/press-releases/2021/Guardant-Health-Expands-Guardant360-Portfolio-With-New-Tests-for-Treatment-Response-Monitoring-and-Complete-Genomic-Profiling/default.aspx#:~:text=The Guardant360 Response™ test,a patient's response to treatment.). Believe this is a fairly new technology, but is supposed to give earlier indication at the molecular level as to whether the levels of CtDNA are rising/decreasing (which I understand to be directly correlated to immunotherapy response). The benefit being, doctors would be able to tell much earlier than via RECIST (traditional monitoring via scans), whether the current treatment is working, or whether they need to pivot quickly to another alternative. I'm not 100% on that, but that is what I understand based on the research I've been doing on my own.

Again, thank you all and appreciate all of the positive vibes and prayers.