Globally sarcomas account for about 1% of all adult cancers, and between 15-20% of paediatric cancers. In the US, 17,000 new cases are diagnosed each year, resulting in around 7,200 deaths from the disease. In the UK, each year about 4,300 people are diagnosed with a soft tissue sarcoma, and 550 are diagnosed with bone sarcoma. Sarcoma is considered one of the deadliest rare cancers.
Sarcomas are a rare and heterogeneous form of cancers that develop in connective tissues like bone, muscle, fat, and cartilage. There are over 50 identified subtypes., some more common forms include: osteosarcoma, Ewing's sarcoma, rhabdomyosarcoma, liposarcoma, angiosarcoma, and gastrointestinal stromal tumours.
Patients with sarcoma can experience a range of symptoms depending on where the sarcoma is located, these range from swelling, broken bones, fatigue, weight loss, to a new lump forming.
Treatment depends on the sarcoma subtype and stage, but can include surgery, radiation, and chemotherapy. Prognosis varies greatly by sarcoma subtype from highly curable to very aggressive.
There are over 200 active clinical trials for sarcoma listed on clinicaltrials.gov in the United States (a drop in the ocean against the 65,000 active studies listed). Many of these trials focus on soft tissue sarcomas, and are sponsored by academic institutions, biotechs, and nonprofits.
“Most importantly–never give up HOPE” – Ian, osteosarcoma patient (Sarcoma Foundation of America, Patient Stories)
Clinical Trial Challenges
There are several contributing factors which make clinical trials for sarcoma challenging to conduct.
Sarcomas are rare cancers, with an estimated 17,000 new cases per year in the US. The small patient population makes recruiting enough participants to thoroughly investigate a new candidate difficult.
There are over 50 subtypes of sarcoma. Each subtype needs to be studied separately to draw valid conclusions. This further segments the relatively small patient pool.
Sarcoma subtypes vary significantly in genetics, growth rates, metastasis rates, and more. This means that responses to treatment can be hard to predict.
As a rare disease, sarcoma research struggles to attract major funding from pharmaceutical companies and large research organizations.
Sarcoma patients are widely dispersed – there is no hub of patients, this means that for clinical trials multiple sites will need to be enrolled, across a wide geography. This can make trial supply logistics more complex.
Trials often have strict requirements around patient age, subtype, treatment history, tumour stage. This further limits eligible participants per trial.
Endpoint selection: Overall survival is difficult to use as an endpoint given the heterogeneity. Surrogate endpoints are not always validated.
“Stay positive! I live by that mantra because I believe I would not be here today if I had not been able to keep my positivity throughout my entire fight“ – Robert, Ewing's sarcoma patient (Sarcoma Foundation of America, Patient Stories)
Active Sarcoma Research
Pfizer - Testing lorlatinib and dacomitinib across sarcoma subtypes.
Eli Lilly - Trialling olaratumab, ramucirumab, and CYRAMZA (ramucirumab) for soft tissue and bone sarcomas.
Novartis - Studying pazopanib, Votrient, and famitinib for use in sarcomas.
Bayer - Testing regorafenib and Stivarga for treatment of gastrointestinal stromal tumours.
Epizyme - Developing tazemetostat for epithelioid sarcoma and other INI1-deficient tumours.
Daiichi Sankyo - Studying pexidartinib and quizartinib for tenosynovial giant cell tumours.
Immune Design - Testing novel immunotherapy approaches for various sarcoma subtypes.
Karyopharm Therapeutics - Developing selinexor and eltanexor for sarcomas.
Arog Pharmaceuticals - Running trials combining crenolanib with other agents.
GlaxoSmithKline - Studying new uses for Votrient (pazopanib) in soft tissue sarcoma.
Foundation Medicine - Developing genomic profiling tests to enable biomarker-driven sarcoma trials.
“AWARENESS is key!” – Anna, Ewing's sarcoma patient (Sarcoma Foundation of America, Patient Stories)
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