A paper published today in the Journal of Clinical Oncology shows that adding interferon after standard chemotherapy and surgery does not improve outcomes for patients with osteosarcoma.
The EURAMOS-1 trial examined whether adding 18 months of extra treatment after the standard treatment could improve outcomes for patients with osteosarcoma. Osteosarcoma is type of bone cancer. It is rare, with only two to three new cases each year per million people. It mainly affects young adults, adolescents and children. Currently, the standard treatment is intensive chemotherapy with three drugs called MAP (methotrexate, doxorubicin and cisplatin), followed by surgery, followed by further chemotherapy with MAP. The results published online today relate to those people whose tumour had responded well to chemotherapy before their surgery. It compares two randomised groups:
- 359 patients who were allocated to 4 cycles of MAP chemotherapy after their surgery
- 357 patients who were allocated to 4 cycles of MAP chemotherapy followed by weekly pegylated interferon-α-2b (Peg-Intron) for 74 weeks
Interferon is produced naturally in the body, and has been found to be an effective treatment for some cancers. In EURAMOS-1, interferon was injected under the skin. The average age of people taking part in EURAMOS-1 was 14 years old. The disease had spread to other parts of the body in 12% of those taking part.
The results showed that adding interferon after the standard treatment did not significantly improve the event-free survival. Event free survival was the length of time participants survive without:
- the disease coming back again
- the disease getting worse
- new tumours developing
The results are complicated because almost quarter of patients randomised to receive interferon did not start taking it, mostly because they chose not to. Furthermore, four in every 10 patients who started interferon stopped early, almost half because of side effects, and a quarter because their disease had worsened. Half of patients on interferon needed to cut the dose of interferon, or delay it, and half of patients who started interferon experienced severe side effects. Most of these side effects were blood problems.
Together this means that the average dose of interferon received by patients randomised to receive it was much lower than planned. This may be why the trial was unable to see a clear benefit from interferon.
The results of EURAMOS-1 do not support adding interferon to the standard treatment for patients with osteosarcoma. They also suggest that, after six months of standard treatment, children and young people who have responded well to chemotherapy are not keen to have weekly injections for another 18 months. Follow-up is continuing, to help us understand the long-term effects of these treatments.
Those whose tumour had responded poorly joined a separate comparison. They were randomised to receive either standard post-operative chemotherapy, or standard post-operative chemotherapy plus two extra drugs (ifosfamide and etoposide). These will be reported separately. Data altogether on the 2,260 patients who joined the study from Europe and North America were presented at the ASCO Annual Meeting 2015.
Randomised controlled trials are vital to finding out how best to treat patients. Carrying out trials in rare cancers, such as osteosarcoma, is challenging, as it is hard to recruit enough participants to be able to see if a new approach is effective. EURAMOS-1 is the largest osteosarcoma study ever conducted. This shows that it is possible to do ambitious trials that answer important questions for rare diseases, through international collaboration.