Citations and cases for Keytruda or Oprdivo application request for off label use in ASPS patients (updated 2022)

[Olga]

If you need to get Keytruda or Opdivo prescribed off label - providing that you live in a country where they are approved for other indications already and available for other cancer patients.
This is the file we compiled based on the Keytruda (PD-1 block, pembrolizumab) activity data in ASPS patients taken from the publications, meetings abstracts and the personal communication with the responding ASPS patients in Canada.


Canadian ASPS Patients on PD-1 / PD-L1 inhibitors

ASPS patient case 1 from Toronto area, Dx May 2015 with the large unresectable primary tumor in the (paralumbar mass 7*8 cm) and very multiple bilateral lung metastases largest 10-15 mm. Several metastases in skull, largest being 1.5 cm.
Cediranib NCT01391962 May 22, 2015 to Sep 8, 2015. Received 25 rounds of IMRT (radiotherapy) to primary Nov 2, 2015 to Dec 7 2015. 25 rounds. Radiation was recommended by his oncologist, Dr. Albiruni Razak immediately before the trial. On Atezolizumab (PD-L1 inhibitor) NCT02458638 Dec 31, 2015 to July 2017. Completed ~21 rounds.
His last dose was in May 2017 with the almost complete resolution of the primary tumor and metastases. He had to be taken off the trial due to the colitis he developed, but the response continued with some additional shrinkage in mm range (Oct.2017)


ASPS patient Case 2 from Montreal. Got Keytruda off label/expanded access in Montreal, starting in September 2016. The patient is responding well presently (Nov 2017) with a partial response in many lung metastases and the complete resolution of some of them, plus with the primary tumor responding by PET, size and manual evaluation (reduced density). Elisa’s oncologist is Dr. Palumbo at the Jewish General Hospital in Montreal. Dr. Razak, sarcoma oncologist from PMH recommended adding radiation therapy to intensify the response after the first evaluation has shown stability, which was done after the second dose (IMRT to the primary tumor). Merck’s Patient Assistance Program is paying for the drug.

There are other numerous cases of the durable, long term responses to Keytruda, Opdivo and Tecentriq in ASPS patients residing in other countries (mostly US and China), in the clinical trials setting and off label prescription, the information re. Clinical cases with the contact information of the treating oncologists might be provided if needed.


ASPS & PD-1 publications reporting clinical benefit:

Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial
https://pubmed.ncbi.nlm.nih.gov/31078463/
Axitinib plus pembrolizumab has manageable toxicity and preliminary activity in patients with advanced sarcomas, particularly patients with ASPS

Publications re. activity of the programmed cell death-1 (PD-1) inhibitors in ASPS.

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. "

7. Complete Response to Dual Immunotherapy in a Young Adult with Metastatic Alveolar Soft Part Sarcoma Enabled by a Drug Recovery Program in a Community Practice. (nivolumab+ipilimumab)
https://www.ncbi.nlm.nih.gov/pubmed/31855495
https://cureasps.org/forum/viewtopic.php?p=14784#p14784
8. A Retrospective Analysis of the Efficacy of Immunotherapy in Metastatic Soft-Tissue Sarcomas
https://pubmed.ncbi.nlm.nih.gov/32664595/
9. A durable complete response to immunotherapy in a patient with metastatic alveolar soft part sarcoma
https://pubmed.ncbi.nlm.nih.gov/32664595/
10. Novel therapeutic options for alveolar soft part sarcoma: antiangiogenic therapy, immunotherapy and beyond.
https://pubmed.ncbi.nlm.nih.gov/32541316/
11. PD1/PD-L1 targeting in advanced soft-tissue sarcomas: a pooled analysis of phase II trials
https://pubmed.ncbi.nlm.nih.gov/32430039/
Analysis by histological subtype revealed that patients with alveolar soft part sarcoma and undifferentiated pleomorphic sarcoma exhibited the highest response rates
12. PD-1 blockade using pembrolizumab in adolescent and young adult patients with advanced bone and soft tissue sarcoma
https://pubmed.ncbi.nlm.nih.gov/33314769/
Two patients with alveolar soft part sarcoma received a clinical benefit from pembrolizumab: one had a radiological partial response with an excellent clinical response and one patient achieved stable disease.
13. Blockade of VEGFR and PD-L1 Inhibits Alveolar Soft-Part Sarcoma
https://pubmed.ncbi.nlm.nih.gov/34468385/

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[D.ap]

Olga

This is fantastic !
Thank you for consolidating
All this !
Love
Debbie

[Bonni Hess]

Dear Olga, Thank you for graciously sharing this very well written, well researched, and well documented Keytruda application request which will certainly be extremely helpful and beneficial to ASPS Community patients and their families who are seeking off label use of this very promising new drug. Shared information like this remains critically important in fighting this extremely rare disease, and I remain deeply grateful for all of your ongoing invaluable shared researched and anecdotal experience information and extensive ASPS knowledge. With deepest gratitude and appreciation and continued Hope, Bonni

[Olga]

To get an access to Keytruda off label, your oncologist would need to agree to prescribe it to you off label and contact Merck reps in your country to get an access to this drug on an expanded access program
http://www.msd.com/contact/contacts.html#s

[D.ap]

Olga

Opdivo now FDA approved for metastatic small cell lung cancer .


An interesting side note to the trial that accerated the ICI approval—


“Results from a blinded independent central review showed 12% (95% CI, 6.5-19.5) responded to treatment regardless of PD-L1 expression.”

And

“Small cell lung cancer can be a very challenging disease, particularly for those who have already been through multiple types of treatment, as most patients relapse within a year of diagnosis,” Andrea Ferris, president and chairman of LUNGevity Foundation, said in the press release. “This approval marks a major milestone for the patients touched by this unrelenting disease and may motivate them to pursue further treatment where there previously were no other approved options.”




https://www.healio.com/hematology-oncol ... ung-cancer




“What is the survival rate of small cell lung cancer?
The 5-year relative survival rate for stage III SCLC is about 8%. SCLC that has spread to other parts of the body is often hard to treat. Stage IV SCLC has a relative 5-year survival rate of about 2%. Still, there are often treatment options available for people with this stage of cancer.May 16, 2016”


And last but not least
The move from PDL1 markers to
tumor mutational burden(TMB) markers-

http://www.ascopost.com/issues/july-10- ... ng-cancer/

[Olga]

I think that the same letter can be used for both, Keytruda and Opdivo off label requests as some of the articles used are based on Keytruda, some on Opdivo and some use both drugs in the analysis. They both are approved for other (not ASPS) indications, and they both are noted to be active in ASPS with supportive articles avail. It is up to patients to seek an access to the treatment, the oncologists are busy and sometimes under the pressure from their regulatory bodies not to prescribe the drug off label, esp. if it is paid by the insurance or by the local government health system as ICI drugs are very expensive. In some countries, the companies are allowed to provide this drugs free of charge if they choose to based on preliminary evidence of efficacy and they want to collect off trial data for the efficacy to facilitate the approval in that disease, in some countries they would not consider that or are prohibited and it creates a problem for the patient. Si it needs to be investigated. Some times it is easier to get Opdivo than Keytruda, or cheaper. We have no reason to consider one being more efficacious for ASPS than another as they are essentially the same. There are few ICI drugs that are more specific (atezolizumab etc), with less supporting articles avail. but they are also active in ASPS.

[D.ap]

Bump