Inform, Empower, Connect

The FOSTER consortium (Fight Osteosarcoma Through European Research) aims to connect clinicians, researchers, and patient advocates across Europe to improve clinical research in Osteosarcoma (OS).

In this research, members of the FOSTER Consortium looked at OS clinical trials that were published over a period of 19 years.  This is to gain an understanding on the treatment strategies for people with OS that has returned after it has been treated (recurrent OS) or OS that does not respond to treatment (refractory OS). These types of OS are referred to as RROS.

The outcomes for people with RROS are poor.  The research in this patient group can help develop our understanding. The results can be used to develop new treatments.

What did the researchers do?

Researchers looked at how these clinical trial design and results have shaped newer clinical trials for RROS. To do this they compared clinical trial design and results from 2003 to 2022. A total of 169 trials are included in this review.

Phase II clinical trials were included in this analysis. Treatments included:

  • Chemotherapy
  • Targeted therapy
  • Immunotherapy
  • Radiotherapy
  • Other treatments not included in the above.

Researchers also included the following trial information:

  • Who could and could not enter the trial (such as diagnosis, stage of disease, and age of people)
  • Where the RROS was in the body
  • Trial design (such as if there were different groups within a trial, if the trial was randomized or blinded, and the number of people in the trial) 
  • Reported results, including response and survival rates.

What did they find?

The review of RROS trials found:

  1. The number of trials looking at chemotherapy treatment decreased over time.
  2. The number of phase II clinical trials specifically for people with RROS increased.
  3. The number of trials looking at targeted therapy increased over time.
  4. Immunotherapy trials increased over time.
  5. An increase in child and teenage patients in trials which also included adults with RROS.
  6. There may be a lack of knowledge on the RROS treatment with chemotherapy for trials that look at the combination of chemotherapy with a new therapy. This could affect results.

What are the recommendations for future research?

Research into RROS needs to have more randomised trials. Randomised trials are the ‘gold standard’ for clinical trials because they have better control over different aspects of the trial. Being able to lower differences between trial design and participants would improve results.

These trials can address patient needs by defining a standard treatment pathway for peple with RROS. They can also improve access to new drugs which may be more effective in treating the condition.

Development of biomarker trials would be beneficial. These trials would select people who are suitable for specific treatment plans based on biological markers in test results.  This means targeted therapies would be given and would aim to increase effectiveness of RROS treatment.

Glossary

Phase II clinical trials: randomised and controlled studies looking at the effectiveness and safety of the use of a treatment for a targeted clinical population (in this case, RROS patients).

Recurrent Osteosarcoma: Osteosarcoma which has returned after an initial response to treatment.

Refractory Osteosarcoma: Osteosarcoma that has not responded to treatment.

Randomized trial: Participants are randomly allocated to a group in each part of the trial (eg, treatment 1 group vs treatment 2 group). This is to help control for aspects that are not part of the study.

Blinding: Blinding in trials is where the participant is not told which treatment they are receiving. Double blinding is where both the participants and the clinical staff are not told which treatment they are receiving. This is so the results are not influenced by knowledge or expectations of treatment on either the patient or clinician’s behalf.

References:

  1. Van Ewijk R, Cleirec M, Herold N, le Deley M-C, van Eijkelenburg N, Boudou-Rouquette P, et al. A systematic review of recent phase-II trials in refractory or recurrent osteosarcoma: Can we inform future trial design? Cancer Treatment Reviews. 2023 Nov;120:102625. doi:10.1016/j.ctrv.2023.102625