The ground breaking results of Canadian Cancer Trials Group (CCTG) CO.26 study were presented at the American Society of Clinical Oncology 2019 Gastrointestinal Cancers Symposium (ASCO GI). This Canadian study is the first randomized clinical trial to demonstrate an overall survival benefit for immune checkpoint therapy in patients with colorectal cancer whose tumours were not mismatch repair deficient (dMMR).
In cancer treatment one of the most exciting discoveries over the last few years is the effectiveness of Immunotherapy (IO), drugs that stimulate the immune system fight cancer. The use of IO drugs to either stimulate or remove natural feedback inhibition of the immune system has been shown to be effective in treating some cancers. Unfortunately colorectal cancer has generally proven to be resistant to these types of treatments, except in the 5-10% of patients whose tumours have DNA repair deficiency, known as deficient mismatch repair (dMMR). IO drugs have not previously been shown to help the 90-95% of colorectal patients without dMMR tumours.
“The purpose of the CO.26 study was to compare the effects on colorectal cancer that had become refractory to all standard available treatments of two new Immunotherapy drugs, durvalumab and tremelimumab, says Dr. Eric Chen, CCTG CO.26 study chair and medical oncologist at the Princess Margaret Cancer Centre in Toronto. “These drugs have shown evidence of synergistic effect that we were hoping would 'overcome' the apparent resistance of colorectal cancer to immunotherapy in patients who had exhausted all other standard therapies.”
“Virtually all the patients on the study did NOT have dMMR tumours (their tumours were considered microsatellite stable) and the results shown from this combination of drugs were therefore uncertain as benefits have not been seen in colorectal patients treated with only one immunotherapy drug” says Chris O’Callaghan, Senior Investigator at the Canadian Cancer Trials Group.
Across Canada 180 patients were enrolled at twenty-seven centers between August 2016 and June 2017. One of those patients was Ms. Lucy Chang who was offered the opportunity to participate in the trial after exhausting her other treatment options.
“I felt more comfortable knowing that this was a phase II trial so some benefit must have been seen in earlier testing. I personally experienced few side effects which was important to me as chemo had been hard on my system,” she says of her experience on the trial. “Over the past 18 months I have been able to lead a more normal life while controlling my cancer which has been important me and my family.”
About the CCTG CO.26 trial
A phase II randomized study of durvalumab (D) plus tremelimumab (T) and best supportive care (BSC) versus BSC alone in patients (pts) with advanced refractory colorectal carcinoma (rCRC).
The CO.26 study met its primary endpoint of demonstrating improved overall survival in those patients who received durvalumab + tremelimumab versus those patients who received best supportive care measures only, without adversely affecting patients quality of life. This is the first study demonstrating immune checkpoint blockade effectiveness in colorectal cancer patients unselected for mismatch repair deficiency and suggests that phase III confirmation is warranted.
Eric X. Chen, Derek J. Jonker, Hagen F. Kennecke, Scott Berry, Felix Couture, Chaudhary E. Ahmad, John Goffin, Petr Kavan, Mohammed Harb, Bruce Colwell, Setareh Samimi, Benoit Samson, Tahir Abbas, Nathalie Aucoin, Francine Aubin, Sheryl Koski, Alice C. Wei, Nadine M. Magoski, Dongsheng Tu, Jonathan Loree, Chris J. O’Callaghan
What is mismatch repair deficiency (dMMR)?
Mismatch repair is a DNA repair pathway that primarily repairs DNA errors that arise during the normal course of DNA replication and as a result of normal cellular metabolism. Deficiency in the mismatch repair process (dMMR) renders a cell unable to repair mistakes made during the cell division process, leading to accumulation of errors in the DNA.
|CCTG CO26 dream team at GI ASCO San Francisco! Supporting Dr. Eric Chen(Princess Margaret Cancer Centre) presenting the CO26 study results. Supporting are Chris O'Callaghan (CCTG) Dr Jonathan Loree (BC Cancer) and Dr Derek Jonker (Ottawa Hospital) #GI19|