Regorafenib may offer patients with refractory gastro-oesophageal a better chance
A collaborative research group led by Australians may have found a glimmer of hope for patients with advanced refractory gastro-oesophageal cancer.
The Australasian Gastro-intestinal Trials Group’s INTEGRATE IIa trial tested regorafenib (Rego) against placebo in a phase II randomised trial with 251 patients from five countries and found a 12-month survival of 19% versus 6% for placebo.
“This study provides hope in a difficult situation. It opens up the door to new research, which we’re already undertaking, and it demonstrates that you shouldn’t give up,” lead author Professor Nick Pavlakis, a medical oncologist with the University of Sydney’s Northern Clinical School, told Oncology Republic.
To be enrolled in the study, patients must have failed or been found intolerant to a minimum of two lines of prior anti-cancer therapy, including a platinum agent and a fluoropyrimidine analogue. Patients were randomised to receive either regorafenib 160mg or placebo, with best supportive care provided to each arm. The median overall survival was 4.5 months for the group who were given regorafenib compared to four months for the group who weren’t.
Professor Pavlakis described the results as “another incremental improvement”.
“If you look back two years, when we started this program, there were only two lines of therapy. Now we are on to five lines of therapy. If you’re lucky to benefit from every single one, you’re going to be the person that can survive the longest with a disease that otherwise would have got people within a year.”
Professor Pavlakis said about 19% of patients on the drug survived a year or longer. Gastric cancer is the fifth most common cancer, accounting for nearly 6% of all new cases and, as the fourth most common cause of cancer-related mortality worldwide, causes almost 8% of all deaths. For patients with advanced refractory disease the prognosis is poor, with a median overall survival of less than six months and real-world data in stage IV disease associated with a two year overall survival of less than 10%.
“Clearly, there is a subgroup that benefits more, but at the moment we have no predictive factor to know who that group is. If you are a patient who is benefitting [from treatment with Rego] it becomes obvious within a couple of months. You would notice that the symptoms of the cancer are stable, whereas in those who do not benefit the disease starts to move very quickly.”
Quality of life was maintained for those who responded to the drug, said Professor Pavlakis. “If you’re enjoying reasonable quality of life, and you try this drug and the side effects are minimal, that’s a worthwhile benefit,” he said.
Buying more time, even measured in months, also meant an opportunity to benefit from research and treatments on the horizon, Professor Pavlakis noted.
“And it gives you the chance to take care of unfinished business with your family, some things on your bucket list that you have not done,” he said.
Professor Pavlakis said the results of INTEGRATE IIa paved the way for testing combinations of Rego with other medications. It also demonstrated the ability of independent collaborative Australian research groups to lead international trials.
The group ran the trial with a grant from the pharmaceutical company and took it up to the stage where the company could commence the subsequent processes of registration and so on.
“As a collaborative group, our purpose is to explore the science, progress the field and find innovation. And the company said yes, we’d like to use that. … That is novel because that success isn’t common and that opportunity doesn’t present itself very often,” said Professor Pavlakis.