Daniel D in South Korea - Dx 2013

[danieldew7]

Hi Olga,

Thanks for the further clarification. I forgot to mention before, my onco told me that monoclonal antibody medication is not compatible for me unlike Ivan or Prairie, however, I will still mention it again especially for nivolumab and pembrolizumab. Other than the 50mm in my left shoulder (It supposed to be inside my lymph), there are few mets in right lung, the biggest is 20mm and the presumed mets in the adrenal gland. Left lung is still clear after surgery last year.

Thank you,
Daniel D.

[Olga]

in that case 20 mm met would def. qualify you for the clinical trial, so they have something to measure.
I am not sure what did you mean, that monoclonal antibody medication is not compatible for you unlike Ivan or Prairie? Ivan did not have the PD-L1 expression measured. And it is already found not to be a complete prognostic factor for many cancers response. They say that higher expression tumors have better chance to respond, but in many cases tumors with the low expression still respond very well.
The immune-checkpoint inhibitors are a separate class of drugs, monoclonal antibodies are to wide of a definition in this context.

[danieldew7]

Hi Olga,

Doesn't Ivan get pembrolizumab and it is still working for him?
Well noted regarding the onco comments that monoclonal antibody drugs do not work for me.
Together with left shoulder mets surgery possibility, I will ask later whether there is any other checkpoint inhibitor drug work possibility, and why he suggest TKI inhibitor (pazopanib) instead.

Thanks,
Daniel D.

[Olga]

Ivan is on pembrolizumab (Keytruda), PD-1 inhibitor - one of the immune-checkpoint inhibitors, immunotherapy from Merck. His PD-l1 expression was not measured . the test for it is considered to be not reliable and the positive expression does not guarantee the response and the negative expression does not mean there will be no response, just a bit less probable one. Variable results in variable cancers.
Is one of the clinical trials you posted offered to you or not? 2, 3 and 4 are for the same class of drugs but more specific ones.

[danieldew7]

Hi Olga,

The clinical trials are not offered for me, it's just what available right now for sarcoma type cancer in here.
Unfortunately, I still haven't found clinical trial for K in here, I still have to ask my onco regarding its availability.
Understood about the immunotherapy compatibility test and its real application difference. Thanks a lot for some clarification regarding that.

Thanks,
Daniel D.

[Olga]

Do not limit the search by pembrolizumab. Any PD-1 or PD-L1 inhibitor is a good choice. Also try to get it off label, not on a clinical trial.

[D.ap]

Hi Daniel
There are plenty of case studies under the ICI section of this forum , to bring to your lead oncologist to ask for an immune check inhibitor off label for you .

Here’s Mario’s story as one case -
On durvalumab


viewtopic.php?f=88&t=1400

[Olga]

Just to give you an article to share with the oncologist as it seems that he suggest the PD-1/PD-L1 testing might be a determining factor to get the immune-checkpoint inhibitors.
Patients with CR/PR to PD-1 blockade (n = 3) had no clear correlation with PD-1, PD-L1 or lymphocyte markers
Immunoprofiling in alveolar soft part sarcoma.
ttps://ascopubs.org/doi/abs/10.1200/JC ... uppl.11059

Background: Alveolar Soft Part Sarcoma (ASPS) is a distinctive tumor characterized by a canonical ASPL-TFE3 fusion. Treatment options are limited. We assessed tumor immune cell infiltrates, and correlated this with patients receiving PD-1 blockade. Methods: A retrospective institutional review was performed for 18 cases of ASPS. Immunohistochemistry was performed on paraffin-embedded tissue (PET) for T-lymphocyte markers (CD3/CD4/CD8), and PD-1/PD-L1 (Ventana). Expression was quantified by standard methods: (total cells per high power field: score; 0:0; 1-10:1; 11-50:2; 50-99:3; 100:4). Select cases underwent DNA sequencing analysis using whole exome (WES, > 80X, n = 4) and genome (WGS, > 30X, n = 1) sequencing. Indel analysis was conducted via mutect2 ( > 5% variant allele frequency) and mutational signature was performed using deconstructSigs. Results: The median age was 27 (15-54). Disease status at diagnosis was: 44% localized; 56% metastatic. The median overall survival was 17 yrs (2.9-31). Four patients (pts) received immunotherapy with PD-1 blockade with 1 complete response (CR), 2 durable partial responses (PR) and 1 stable disease (SD). PET was available in 12 cases. PD-1/PD-L1 expression (≥1) was seen in 50% and 17%, respectively. Composite CD3, CD4 and CD8 infiltration were 2, 1, and 1, respectively. Patients with CR/PR to PD-1 blockade (n = 3) had no clear correlation with PD-1, PD-L1 or lymphocyte markers. Exomic characterization (n = 4) demonstrated no clear excess mutation burden compared to Ewing sarcoma (5.7 vs 6.4 mut/MB). Mutational signatures via COSMIC were identified in the mismatch repair (MMR) pathway in 2 of 4 cases (Pt A: Signature (S) 26; pt B: S6 and S15). Pt B also underwent WGS which confirmed a COSMIC signature in the MMR pathway. Indel analysis did not confirm aberrations in standard MMR or polymerase genes. Conclusions: Preliminary findings suggest activity with PD-1 blockade in ASPS; however, this does not appear to correlate with tumour-infiltrating T lymphocytes. Genomic analysis suggests an MMR signature may account for these responses, but standard MMR aberrations were not identified. Further validation is underway.

[D.ap]

Daniel and Olga
Took the liberty of correcting the ASCO link-

https://ascopubs.org/doi/abs/10.1200/JC ... uppl.11059

Also link to COSMIC ( catalogue of somatic mutations in cancer) for your team , Daniel

https://cancer.sanger.ac.uk/cosmic

[danieldew7]

Dear Olga and Debbie,

Today my onco found another skull mets on right side after last month's MRI.
The met is still small so he recommends surgery within this month.
Attached images are comparison from May skull mets and this month mets.
May:
https://ibb.co/4TxRKcL
November:
https://ibb.co/r45SM7h

Best regards,
Daniel D.

[D.ap]

Hello Daniel
I’m sorry you are seeing what appears to be a new appearing image to your brain MRI.
Just after we started on Opdivo in 2017, Josh had a skull bone image appear. After 4 months on Opdivo , it resolved. By Opdivo alone .
I wouldn’t want to give you false hope by telling you this and steer you away from your surgery but what about your adrenal gland pursuit ?

This is our experience -

viewtopic.php?f=4&t=750&hilit=Skull&start=180#p10252

How are you doing with that research?

It really seems that you will need a systemic Med sooner than later ,and immunotherapies( ICIs) are showing great success with a lot of ASPS patients these days . And the beauty of ICIs are that they can be used with other treatments like Ie SRS and or IMRT (radiation therapies ) cyroblation to increase the systemic immune response, without interruption during these possible , adjunctive treatments . Abscopal affect.
Maybe on your lymph node tumor ?

[danieldew7]

Hi Debbie,

No- not really at all! Thanks for the suggestion, now I have nivolumab added on the list for adrenal gland possible treatment.
The systemic treatment will be planned next January, the new met on my right skull is still small and my onco. definitely wants to remove it while it is still small, just in case the systemic treatment doesn't work for me, because surgery post-chemotherapy is not easy. The surgery itself will be done this month.

Thanks,
Daniel D.

[ntran727]

Hi Daniel,

I agree with Debbie and Olga that you should try to get an ICI drug (Immune Checkpoint Inhibitors. There are many in this class, including:

CTLA-4 inhibitor:
ipilimumab (Yervoy)

PD1 inhibitors:
Pembrolizumab (Keytruda)
nivolumab (Opdivo)

PD-L1 inhibitors
Atezolizumab (Tecentriq)
avelumab (Bavencio)
durvalumab (Infimzi)

The popular ones used are Keytruda, Opdivo, and Tecentriq but I have seem most of them used by an ASPS patient either in trial or off label. There are also combos of TKI + ICI drugs that are used in trial. The TKI drugs do work for some patients but usually temporarily. I was on Sutent and had stability for 2 years, then developed bone Mets. I went on Keytruda which did not work for me initially, so we added back a different TKI (pazopanib). I also had SBRT to one of my bone Mets to try and achieve the abscopal effect (where radiation when given in combo with the ICI drug can lead to better detection of the tumors to increase its effectiveness). I ended up very sick but something about the combo triggered response. My Mets have all been stable since then and I am continuing pazopanib until we can decide if I should resume the ICI drug. My hope is to eventually resume it because I think that was the main drug that worked, however hard to say if it was the combo of TKI + radiation + Keytruda or if Keytruda would’ve worked alone.

Either way, many have had good responses with ICI drugs with long term response vs. TKIs (Sutent/pazopanib).

I would recommend removal of the shoulder tumor If it is easily resected since it is quite large and can increase your tumor burden and lead to less response to systematic therapy. I would ask about gamma knife to the skull met as surgery is much more invasive depending on the area. If possible to start an ICI drug right after gamma knife, it may produce the abscopal effect. Olga can elaborate more about that.

Hope you get your treatments sorted out soon!


-Nhi

[danieldew7]

Hi Nhi,

Thank you for the information!
I know one patient who gets Ipilimumab and Nivolumab combo but still waiting for response, as during the treatment there is new met found on his spine. Don't mean to discourage the use of this drug since it could be there before.
After discussing with Debbie and Olga, and read several posts regarding target therapy, I think I could ask for Durvalumab, Pembrolizumab, Nivolumab availability first, and should there is any option for me to use Atezolizumab and Avelumab as well.

Best regards,
Daniel D.

[danieldew7]

Dear all,

After asking about -mab medication, my onco didn't recommend taking anything on this point.
He told me to remove the mets in left collar bone lymph since the size is quite stable lately, but with no reduction.
Next meeting will be on 20th next month and surgery will be performed after that.
Last week bone scan result didnt show any symptom and mets in right lung is still the same.

Best regards,
Daniel D.