Cure Alveolar Soft Part Sarcoma International (iCureASPS)

ABSTRACT
Immune checkpoint inhibitors (ICI) are an important development in the treatment of advanced cancer. A substantial proportion of patients treated with ICI do not respond, and additionally patients discontinue treatment due to adverse effects. While many novel biological markers related to the specific mechanisms of ICI actions have been investigated, there has also been considerable research to identify routinely available blood and clinical markers that may predict response to ICI therapy. If validated, these markers have the advantage of being easily integrated into clinical use for nominal expense. Several markers have shown promise, including baseline and post-treatment changes in leucocyte counts, lactate dehydrogenase and C-reactive protein. While promising, the results between studies have been inconsistent due to small sample sizes, follow-up time and variability in the assessed markers. To date, research on routinely available blood and clinical markers has focussed primarily on ICI use in melanoma, the use of ipilimumab and on univariate associations, but preliminary evidence is emerging for other cancer types, other ICIs and for combining markers in multivariable clinical prediction models.

Keywords: immune checkpoint inhibitors, precision medicine, biomarkers, clinicopathological, melanoma

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625676/

A phase II trial of axitinib plus pembrolizumab for patients with advanced alveolar soft part sarcoma (ASPS) and other soft tissue sarcomas (STS).

ASCO 2018

Correlative markers were analyzed by a penalized logistic regression model with bootstrapping to predict PFS3mo. Baseline high plasma angiogenic activity, circulating neutrophil:lymphocyte ratio < 4.1, low naïve fraction CD4+ TIL, and low PD1+CD8+ PBMC were associated with lack of progression (AUC 0.878 [95% CI 0.743-1, p = 0.0002]).
https://meetinglibrary.asco.org/record/162020/abstract

If I remember correctly pd1 and ctla4-inhibitors only achieved 40 percent response rate. So looks like pd1-inhibitors should be combined with tki instead of ipilumab. As most effective tki in asps is cediranib and based on ovarian cancer studies cediranib is safe as long as diarrea can be managed without hurting gut microbiome as imodium can also effect gut microbiome I stopped using it once I started immunotherapy and now I only use dried blueperries.

If I understood correctly high amount of lymphocytes would be beneficial, which makes sense as natural killer cells are effective against cancer and they are lymphocytes.

High angiogenetic agtivity is associated with good response, explains why immunotherapy works well in asps. That question has been driving me crazy.

I might have understood everything wrong.

I would love to see trial combining cediranib, pd1-inhibitor and hypofractoned radiation if there is metastases that can savely targeted to create abscopal effect in asps. Based on current evidence, I believe, that combination is justified. As Astrazeneca has pd1:n ligand targeting drug it could sponsore whole trial. As results would almost certainly be good, it would make Astrazeneca look really good and they would pracically gain monopoly in asps treatment. Of course asps is very rare, but patients live long, so this would allow company to sell very expensive drugs for years.

ASPS patients have no value for any pharma company. Our dear patient Katrina from UK had to flight the AZ when they were going to stop cediranib production despite it being very active in ASPS, and it was US health authorities that sponsored the drug for it to continue (National Institutes of Health (NIH)).