Daniel D in South Korea - Dx 2013

[Olga]

The text that we used when applied in Canada for Keytruda off label (means it is approved for other cancers but we were asking to provide and pay for it based on the rare disease situation when there are reports and ongoing clinical trials but they are to slow due to a limited enrollment):
http://www.cureasps.org/forum/viewtopic.php?f=76&t=1482
The same letter can be used for other immunoitherapy drugs - Opdivo, Keytruda etc.
The drug he offered to you is approved for all sarcomas now - and I have no idea why as there is no Phase 3 clinical trial to support that either.

[danieldew7]

Dear Olga,

Yes I already discuss about Pembrolizumab (Keytruda), Anlotinib, Cediranib, Sunitinib (Sutent), Pazopanib (Votrient) but my onco said that while there is reducing case, but 5 years survival rates are only 0~5% for them.
Should the mets really spread further, he suggest Doxorubicin + Ifosfamide but doesn't recommend them for my current state.
So after other immunotherapy and laser surgical discussion, my onco does not suggest them because they only delay the progression.
Looking at long term survival rate (long tail result), he choose Doxorubicin (Adriamycin) + Olaratumab (Latruvo) at following schedule starts from yesterday:
[1st cycle]
Day 1 Doxorubicin + Olaratumab
Day 8 Olaratumab
Day 24 Doxorubicin + Olaratumab and body scan (blood test, x-ray) to consider 2nd cycle or other medicine

[D.ap]

Daniel
What sarcomas, are your doctors comparing their data to as a basis?

[Olga]

I second Debbie question. Ask him to provide the publication to confirm there were any ASPS patients and that they had any beneficial effect from this combination. I do not think so.
Also where did he get the data re. survival on Keytruda or Opdivo if the clinical trials are not done/finished yet? I think he is not correct. Ask him to provide you the published studies to confirm what he said.
Also re. cryo or radiosurgery ONLY delaying the progression. It is GREAT when something can even delay the progression, the treatment he offers would mot probably not even delay the progression, ask him what is the expectation the treatment he proposes can do and to prove it with any publication. ASPS is a slow growing disease and delaying the progression may in fact enable you to survive long enough for the Keytruda or Opdivo or other drugs be approved for ASPS and be covered by the insurance.

[danieldew7]

Dear Debbie and Olga,

Yes it is as both of you stated that the clinical trial is not done yet but he insist that olaratumab is the best option for now.
I already ask for the clinical data just as you suggest but my onco. did not give it to me because the data is not finished yet.
Well why didn't he gave me that unfinished data.. but he told me that he cannot share the data.
For ASPS, there are only 30 cases overall in my hospital and previous patients undergo cediranib and sutent and the outcome is not good for long term, that is why he recommend this drug combination for me.
Even I wondering did he only gave the most comfortable choice for me, since every time I ask for the details his answer is so rough and he said that his schedule is very tight.
I will ask to give other details and treatment expectation on my next visit, since I will also could see the progression after scanning then.
Thanks for your suggestion as always!

[D.ap]

Daniel
Here’s an ASCO report on your combination of meds you are on.

http://www.ascopost.com/issues/november ... e-sarcoma/

Were you tested for the PDGFR molecule from one of your tumors?
The tumors are only being seen in your lungs and are below a centimeter ?

[arojussi]

Getting access to immunotherapy can be very difficult as these are very expensive drugs. Interestingly immunotherapy seems to work best against asps. Even better than against melanoma. So Drug company, that is able to test it`s pd1-inhibitor with as many asps patients as possible will have great numbers to show how effective their drug is. So some drug company might be willing to provide some pd1-inhibitor for you to have good publicity.

[danieldew7]

Dear Debbie and Jussie,
Thanks for the article!
My current visible mets is at my left collarbone and back of my skull.
I'm not sure whether they done PDGFR molecule test, they only did CBC, ESR and LDH blood test.

For additional info, my onco already held clinical trial with pazopanib but terminated due to poor follow up and he told me about that.
Link reference: https://clinicaltrials.gov/ct2/show/NCT ... =KR&rank=1
I already pointed some of PD-1 inhibitor drugs but he told me that their response ratio is only 5% at maximum. Well at least he suggest another similar monoclonal antibody drug, no?
Sigh- I do hope this could be success case or at least reach Ms. Sullivan success story level.

[Olga]

Daniel - I do not understand your oncologist suggestion that immune check point inhibitors are 5 % defective? Did you present him all the articles that are published re. immune check point inhibitors (PD-1 inhibitors drugs the other name). 5% is not even close! Generally ASPS patients more often respond to ICI drugs than not.
I copy from the post I linked earlier already - we used this list to get Keytruda paid for by the government here in Canada:
Publications.

We researched both, pembrolizumab (Keytruda) and Nivolumab (Opdivo) as they appear to be interchangeable:
Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable http://dx.doi.org/10.1053/j.seminoncol.2017.06.007
It appears likely that any effective PD-1 blocking agent will have similar clinical outcomes (subject to trial design) and the evidence or lack thereof of efficacy can be combined.

1. Anti-PD1 therapy with nivolumab in sarcoma https://doi.org/10.1093/annonc/mdw388.06
2. PD-1 blockade using pembrolizumab in adolescent and young adult patients with advanced bone and soft tissue sarcoma.
http://ascopubs.org/doi/abs/10.1200/JCO ... suppl.3060
3. Positive Tumor Response to Combined Checkpoint Inhibitors in a Patient With Refractory Alveolar Soft Part Sarcoma: A Case Report http://ascopubs.org/doi/full/10.1200/JGO.2017.009993
4. PD-1 blockade using pembrolizumab in adolescent and young adult patients with advanced bone and soft tissue sarcoma
https://doi.org/10.1186/s13569-016-0064-0
5. Immunoprofiling in alveolar soft part sarcoma http://ascopubs.org/doi/abs/10.1200/JCO ... uppl.11059
6. A phase II trial of axitinib plus pembrolizumab for patients with advanced alveolar soft part sarcoma (ASPS) and other soft tissue sarcomas (STS).

Presented on ASCO 2018 on Saturday, June 2, 2018
https://meetinglibrary.asco.org/record/162020/abstract
" PFS3mo in ASPS pts was 90.9% [95% CI 50.8-98.7], with best ORR of 45.5% [95% CI 18.1-75.4] and CBR of 72.7% [95% CI 39.3-92.7]... Conclusions: Combination Ax/P is well-tolerated with promising activity in ASPS pts. "

[danieldew7]

Dear Olga,
After second cycle of olaratumab and doxorubicin, met in right lung grew 2mm, one in between left collarbone grew 5mm, and on the back of my skull grew a bit, visible but not measured.
The next step is I will get another chest CT and full body bone scan next month, and after discussing your previous opinion, my onco also give future option with pazopanib should the next scan is also detect growth. He also aware of pembrolizumab but it is still unlicensed in Korea.
Any other thought is greatly appreciated.
Thanks!

[Olga]

Is pembrolizumab still unlicensed in Korea at all or for ASPS? Clarify with the oncologist (it is unlicensed for ASPS everywhere and is prescribed off label).
Any other ICI drugs can be substituted or seek a clinical trial as they are all active in ASPS and come are nearly identical:
Nivolumab (Opdivo) - approved in your country for melanoma https://www.thepharmaletter.com/article ... outh-korea
atezolizumab (brand name Tecentriq)
We have a patient on nivolumab (Opdivo) with a good response and the company US branch agreed to provide it to him free of charge on a compassionate basis, contact your local branch to discuss.
The file with the info re. activity of different ICI drugs is posted, use it. Or find out which drug is approved and make a search on the Pubmed to create your own supportive letter.

[danieldew7]

Dear Olga,
Yes I already discuss for pembrolizumab or nivolumab, but my blood test after olaratumab and doxorubicin trial for 2 cycles show that monoclonal antibody (-mab) drug is not responsive, the PD-L1 is negative.
After stop chemo they went for surgical option and last week I got cranial surgery to remove 2cm in diameter of my parietal bone. They checked the brain and it was intact from tumor so they just removed until outer membrane and put back artificial skull about 10cm in diameter in the tumor location.

[D.ap]

Hello Daniel

I sure hope you are doing well after all you’ve been through.

If you wouldn’t mind , what test showed the “mab” pdl1 wasn’t responding to your tumors? The tumors progressed?
If so a lot of these mabs are showing progression before shrinkage sometimes as late as 8 cycles ( 4 months ).
I’ve heard of a patient not seeing response ( shrinkage ) up-to a year from first dose . They were on pembrolizumab and Doxorubicin. They quit the Doxorubicin before they saw results .

Also the Doxorubicin is an antibiotic and they are a know immune suppressor as it kills good gut microbes that aid the immunotherapy in its systemic attack .

I wonder of the reason that doxorubicin is used?
Can it keep a possible autoimmune adverse from happening ? Throttling down the immune system by virtue of antibiotic AND chemo Med .

[arojussi]

Even if pd-L1 is negative check point inhibitors can still work.

[D.ap]

Daniel
I hope today finds you feeling stronger and better. :)
I have some questions in purple ,from your post May 10–

Jussi is correct in his statement as well.

I believe TMB ( tumor mutation burden)is very important in the success of Pdl1 meds success .

https://www.ncbi.nlm.nih.gov/m/pubmed/2 ... 55/related

I believe that is what made nivolumab successful for our son Joshua . We never tested for Pdl1 ( msi)
but jumped in with both feet and never looked back . He was 93lbs and had a 6cm lung tumor , adrenal, liver and a small brain tumor.

Today he’s 130lbs , 1.3cm lung tumor ( multiple have disappeared) and 3 of 4 liver tumors stable since 2016.

Dear Olga,
Yes I already discuss for pembrolizumab or nivolumab, but my blood test after olaratumab and doxorubicin trial for 2 cycles show that monoclonal antibody (-mab) drug is not responsive, the PD-L1 is negative.


What marker are the medical proffessionals looking at that signal you aren’t responding? Or are they going by your shoulder and brain tumor increases ?
After stop chemo they went for surgical option and last week I got cranial surgery to remove 2cm in diameter of my parietal bone. They checked the brain and it was intact from tumor so they just removed until outer membrane and put back artificial skull about 10cm in diameter in the tumor location.

Did they check the resection tumor for affect from the olaratumab ?

Increases can be a response from the the meds , I’m sure you all know .
Also this combo was a step to see if this helped and the brain tumor may hold some clues.
What other tumors have they tested?

This may feel like a failure but there is so much out there to be hopeful for.

Much love