Insights into treating rare cancer tumours benefit patients
What is the best way to tackle sarcomas? Although clinical trials help to generate insight, they are hard to set up for rare diseases. An EU-funded project has organised several trials focusing on these malignancies, providing insight that is already helping to save more lives. It has also paved the way for further research to help patients.
© Mikel Taboada #318544689, source:stock.adobe.com 2020
Sarcomas are a group of rare tumours that typically form in the bones or soft tissue in the arms, legs, or abdomen. While the prognosis for different types of sarcoma varies greatly, treatment is difficult in many cases, and it can have long-term implications for the patient such as the need to use prosthetics following surgery.
Starting from a planned eight clinical trials, the EU-funded project EUROSARC trialled competing options for various aspects of the treatment of different types of sarcoma. Two major studies that were initiated and completed during the project have changed clinical practice for some of these rare cancers, says project coordinator Jean-Yves Blay of Université Lyon 1 Claude Bernard, France.
They notably concluded that one of the approaches studied, for a specific subtype of sarcoma, boosted patient survival by nearly 10 %. This particular study showed that giving patients chemotherapy prior to surgery for large, aggressive sarcomas of the limb improves the quality of treatment and survival, Blay explains. This had never been demonstrated before, and chemotherapy was not extensively used.
The second practice-changing trial focused on a specific group of retroperitoneal sarcoma, the most frequent sarcomas in the abdominal region. Its findings shed new light on a treatment option that involves significant constraints and side effects. It concluded that pre-operative radiotherapy did not improve the outcome for patients operated in reference centres, Blay notes.
Informing clinical practice ...
EUROSARCs other trials explored leads, assessing the effects of possible new treatments as a first step towards potential future research by comparing them to other approaches, Blay adds. For example, such trials are organised to test the effectiveness of medication that is already on the market for diseases other than those for which they were initially developed.
As of January 2020, two of these proof-of-concept trials are still running. Respectively, they are exploring the value of sirolimus and cyclophosphamide in chondrosarcoma, a very resistant form of sarcoma, and that of an antibody, anti-RANKL, in a very rare form of bone tumour (so-called giant cell tumour), Blay explains. Both are based on the identification of molecular targets in the tumour, specifically activated in these rare types.
Another trial, completed prior to the projects end in May 2018, concluded that the treatment on which it focused did not live up to expectations, as did a fourth, which was dropped, Blay notes. These trials had explored the effectiveness of an anti IGF1R tyrosine kinase inhibitor in Ewing sarcoma, with only one patient with long-term efficacy, and an immunomodulatory agent (MTP) in combination with ifosfamide in osteosarcoma.
...and future research
EUROSARC was invaluable in that it enabled us to conduct trials that might otherwise never have been performed, Blay underlines, stressing the difficulties of funding such studies for rare diseases particularly if they are not linked to the development of new drugs.
Other important outcomes, along with the positive and negative results of the trials, include the fact that the project generated new questions to be examined through further study, along with a valuable collection of tumour material donated by patients to support future research.
Follow-on work is already under way. The tissue collected in EUROSARC is being studied to identify genetic alterations that might help to develop personalised treatments.
Furthermore, a new trial is about to be launched by the European reference network EURACAN, a recent addition to the string of projects and networks that have been advancing this line of research with EU support since 2006. SELNET, a Horizon 2020 project launched in 2019, is extending this collaboration to partners in Latin America.
Cooperation across centres and countries is particularly important for trials dedicated to diseases such as sarcoma, as a way to enrol sufficient numbers of patients which fortunately are as rare as the illness itself, and even rarer for its individual subtypes and mobilise the equally dispersed expertise of specialists in their treatment, Blay points out.
European projects help to connect national networks and enable them to be more efficient, he concludes.