Research and advanced sarcoma

The research results reported at ASCO for sarcoma are of special interest this year because of the rise of immunotherapy as a cancer treatment. The expectation is that because sarcomas rely on gene mutations which the immune system fails to recognise it would, like other cancers, respond to immunotherapy. The treatment relies on two approaches, stimulating the immune system to overcome cancer’s ability to evade recognition and to block the ability which tumour cells have to hide from the immune response. This combination of approaches works well with melanoma, although the side effects are challenging and can require in-patient treatment.

Yes, it has been tried with sarcomas, albeit so far in small exploratory studies. The problem is that these explorations are not showing that any benefit results. It is very early days and we must hope that more extensive studies will deliver positive results. Researchers are optimistic but I have been around long enough to be cautious.

All kinds of treatments have been trialled to treat advanced sarcoma. A few individual patients have benefitted each time, I am one of them, but no drug treatment has come through to show the degree of patient benefit that would allow it to replace doxorubicin as the first chemotherapy of choice, the worldwide clinical standard.

Having all our eggs in one basket is not a strategy anyone wants to subscribe to. So research with other approaches to treating advanced sarcoma continues. It is an impressive list:

  • Molecular alterations to doxorubicin to improve its effectiveness and remove side effects
  • Innovative cytotoxic treatments using natural toxins
  • Better understanding of sarcoma mutations with the aim of matching existing or innovative new drugs to treat them
  • Exploring new drugs prospectively based on tumour characteristics, often through so-called basket studies
  • Exploring combinations of treatments which individually don’t quite make it, combining them with doxorubicin or with new drugs
  • Looking for a maintenance therapy which may prevent metastases
  • Developing new non-invasive techniques for removing lung metastases (eg RFA, SABR)
  • Understanding the value of surgery, especially with new techniques such as laser knife
  • Looking at the quality of life for patients with advanced disease, especially when further ‘curative’ treatment would be futile

Some of these approaches are showing positive results. It is increasingly important for clinicians to know the histological sub-type of sarcoma and to have genetic information. Alternative first-line treatment is currently for a small minority so it means that foreseeably patients with advanced sarcoma will continue to face the future with uncertainty.

Only a minority of sarcoma patients develop metastatic disease. Some will have recurrences which are local in their nature and although it is not nice to have to undergo further treatment they can be curable. There is hope the longer you can stay alive, so if the disease starts progressing taking every valid opportunity that arises is a realistic strategy. Our oncologists will be as encouraging as they can be within the bounds of realism when metastases appear. However where choices are offered there is little evidence which will definitively support one treatment approach over any other, although where surgery for metastases is offered my advice is to take it. Surgery is only a valid approach for a small proportion of patients, those with so-called oligometastases.

The annual ASCO event brings together specialists from across the globe, no other cancer event is comparable. Sarcoma is no exception to the rule. While it is exciting to see the range of research which is being undertaken to improve matters for patients it is a sad fact that in bone and soft tissue sarcoma we have not yet seen the kinds of breakthrough that have taken place in breast cancer, leukaemia, kidney cancer or more recently in melanoma. There is the example of GIST, a sensation at ASCO 15 years ago. It shows that it can be done in sarcoma, so there is hope, our specialist scientists and clinical researchers believe it can be done, we have to support and encourage them.