Associate Professors Sumi Ananda & Jeanne Tie
Circulating tumour DNA (ctDNA) testing is being used in RCTs across Australia and New Zealand to determine which patients are at risk of recurrence and their need for chemotherapy after bowel cancer resection.
The RCTs in stage 2 and stage 3 bowel cancer follow on from earlier work which showed more than 80% of patients with detectable ctDNA could expect a recurrence compared to about 8% of patients with no detectable ctDNA.
In the current studies, patients with stage 2 disease are randomised to either standard care or care driven by their ctDNA results. Those with detectable ctDNA receive chemotherapy while those without ctDNA do not receive chemotherapy.
Associate Professor Sumi Ananda, clinician-researcher at the Walter and Eliza Hall Institute (WEHI), and a medical oncologist at the Peter MacCallum Cancer Centre and Western Health, told the limbic that patients in all three arms of the trial for stage 3 cancer will require chemotherapy to reduce their risk of recurrence.
“Once the cancer has spread to the lymph nodes, the clinical trial data in the past has shown that chemotherapy improves the risk of relapse and improves survival.”
“So all patients with stage 3 cancer get chemotherapy but in the randomisation is standard care or ctDNA-guided treatment. If ctDNA positive, then treatment gets escalated. If you were to received single agent chemotherapy, you would now get double agent chemotherapy, or if you were meant to receive double agent chemotherapy, you would get triple agent chemotherapy.”
Patients who are ctDNA negative will still receive standard care.
Associate Professor Ananda said there was more leeway to change management in stage 2 disease and the proof of concept study was compelling.
“Because in stage 2 we still don’t know whether we need to give chemotherapy or not; the absolute risk reduction is only in the order of 2-3% in clinical trials and we are subjecting patients to six months of chemotherapy.”
“I suspect that if what we showed in the proof of concept study holds true in the RCT, this will be practice changing. If our data is robust enough, then certainly patients I’ve seen in the clinic are quite happy to not have chemotherapy.”
“Certainly they are quite happy to be de-escalating treatment or not to have chemotherapy after I show them the survival curves. They are quite happy as the chemotherapy is such a huge burden for six months of their life and their cancer may not recur.”
A proof of concept study for ctDNA testing is also under away in ovarian cancer.
Associate Professor Jeanne Tie, also from WEHI, the Peter MacCallum Cancer Centre and Western Health, said in a statement that the objective was to help patients avoid both short and long-term side effects associated with chemotherapy.
“We would like to be able to tell some patients that they can safely avoid chemotherapy because their cancer is unlikely to recur. For patients who are at a high risk of recurrence, we want to be able to give them a more intensive dose of chemotherapy than those with a lower risk of recurrence,” she said.