Recent success with targeted therapies to treat benign connective tissue tumours has thrown up important questions, says Professor David Thomas from the Garvan Institute of Medical Research.
Using targeted therapies in this way is a completely different scenario to the traditional use in malignant tumours of the connective tissue, he says. “It’s requiring us to rethink how we tackle clinical trials and how we think about the risks and benefits of treatment.”
Speaking at the ESA-SRB 2015 meeting here in Adelaide Professor Thomas told delegates there are now at least two examples of benign connective tissue tumours for which a molecular cause has been identified, and for which targeted therapies may be applicable.
He spoke of how the emergence of the RANKL inhibitor denosumab in the past five years has transformed the management of patients with unresectable giant cell tumour of bone (GCTB).
Also, how more recently another benign connective tissue tumour, tenosynovial giant cell tumour (TGCT), has been targeted with agents blocking CSF-1 signalling, with promising results.
But while denosumab has been spectacular in improving quality of life for patients with GCTB, now after several years Professor Thomas has questions.
“When do we stop treatment, and what sort of long-term consequences are there of using a drug that blocks the signalling pathway that we’re targeting, which turns out to be important for bone metabolism and bone turnover?”
The long-term consequences of treatment haven’t really had to be considered in oncology because treatment with targeted therapies is usually restricted by the lifespan of those with incurable malignant tumours, who are also often elderly.
But both GCTB and TGCT affect a younger population, and are rarely life threatening.
“We don’t have people dying from these diseases and so applying the same sorts of treatment approaches we now have to consider not only whether the drugs improve symptoms and quality of life, but also whether the longer term consequences of treatment justify the interventions,” Professor Thomas told the limbic.
Answering these questions is a work in progress, with the focus on what this means for how clinical trials are conducted. Researchers need to consider how adverse events are measured, how long patients are followed up, what the optimal dosing and scheduling of treatment might be, and how patients are selected.
There are other elements to consider as well. The cost to the community of using these targeted therapies is again fundamentally different from the traditional personalised medicines for malignant disease, explained Professor Thomas.
This is because the duration of treatment is not known and there is no accurate estimate of the numbers of benign tumours that might be referred for therapy, as these tumours are not subject to mandatory reporting and appear to be more common than originally thought.