Tanios Bekaii-Saab, MD
A weekly dose-escalation strategy of regorafenib (Stivarga) is clearly the new standard approach for the agent, as it was found to be superior than the previously average dose of 160 mg in patients with metastatic colorectal cancer (mCRC), said Tanios Bekaii-Saab, MD.
In the phase II ReDOS study, led by Bekaii-Saab, patients were randomized to either the dose-escalation arm—which began at 80 mg daily and increased every week up to 160 mg daily if no dose-limiting toxicities occurred—or the standard 160-mg dose of regorafenib.
Results showed that the median overall survival (OS) was improved in the dose-escalation arm compared with the standard arm at 9.0 months versus 5.9 months, respectively (P
= .0943). The dose-escalation arm also had a slight improvement in progression-free survival (PFS) and quality-of-life data.1
Bekaii-Saab added that nearly double the number of patients made it to cycle 3 of treatment on the dose-escalation arm.
Based on these findings, the National Comprehensive Cancer Network (NCCN) incorporated the dose-escalation approach into their guidelines for regorafenib in this patient population.
Additional data with the multikinase inhibitor were presented at the 2018 World Congress on Gastrointestinal Cancer with the IMblaze370 trial. In the phase III study, the combination of atezolizumab (Tecentriq) and cobimetinib (Cotellic) or atezolizumab alone were not found to be superior to regorafenib in patients with chemorefractory mCRC.2
In an interview with OncLive®
, Bekaii-Saab, a professor of medicine at Mayo Clinic, discussed the ReDOS and IMblaze370 with regorafenib trials in mCRC.
OncLive: Please provide some background to the ReDOS trial.
: We wanted to test how effective the standard dose of 160 mg daily was for regorafenib. It worked for a few patients. For the majority of the patients—let's say 70% to 80%— they were not able to receive the full 160 mg. A lot of the toxicity started to appear in the first 2 to 3 weeks, and it also met its highest severity at that time. That certainly was one of the biggest challenges. Therefore, in the community, a lot of people started using their own schedule and started cutting down on the dose. Some people started with 80 mg and then made their way up to 120 mg. A lot of different alterations were made, but there were absolutely zero data saying that you could alter the dose and keep the same benefit.
This was the premise for ReDOS, which essentially was a randomized phase II study that looked at patients who would be eligible for regorafenib. The experimental arm was a dose-escalation strategy from 80 mg, to 120 mg, to 160 mg on a weekly basis as tolerated. Then you would get a week-long break. Whatever the highest-tolerated dose level was for the first cycle, we would move on to the second cycle. This was compared with the standard 160 mg daily for 1 week on/1 week off. We thought that, for this study, we should have a primary endpoint capturing 2 elements: toxicity and efficacy.
What we did was look at the patients who made it through the 2 cycles and then put them into cycle 3. We're assuming that the dose-escalation arm would be superior because more patients will be able to make it to cycle 3 with that strategy. Our study of 120 patients met its primary endpoint, meaning the dose-escalation strategy of 80 mg, to 120 mg, to 160 mg was superior to the 160 mg daily dose. Almost double the number of patients made it to cycle 3 and continued throughout.