Regorafenib Continues to Benefit Patients With Advanced CRC

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EP: 1.Regorafenib Continues to Benefit Patients With Advanced CRC

EP: 2.Retrospective Data Demonstrates Efficacy of Regorafenib in mCRC

EP: 3.Retrospective Data Highlight Impact of Dose Escalation of Regorafenib in mCRC

Daniel H. Ahn, DO, medical director of the clinical cancer research office, oncologist, and associate professor at the Mayo Clinic in Phoenix, Arizona, discusses the ongoing use of regorafenib (Stivarga) for patients with metastatic colorectal cancer (CRC). Regorafenib is the first small-molecule multikinase inhibitor to show a survival benefit for this patient population and continues to demonstrate effectiveness even with dose modifications.

Regorafenib was approved based on the randomized phase 3 CORRECT trial (NCT01103323), which showed the drug significantly improved overall survival (OS) for patients with metastatic CRC who progressed after standard treatments. The trial investigators recruited 760 patients and randomly assigned them 2:1 to receive regorafenib (n = 505) vs placebo (n = 255) and observed a median OS of 6.4 months compared with 5.0 months (HR, 0.77; 95% CI, 0.64-0.94; P = .0052), respectively.

Following the CORRECT trial, a post hoc analysis of a cohort of Japanese patients on this trial explored if radiological imaging markers could predict clinical outcomes with regorafenib. The analysis, called RadioCORRECT, still showed an improvement in OS and progression-free survival (PFS) for these patients regardless of biomarkers.

Ahn also highlights how the approach to dosing this therapy has changed based on results from the phase 2 ReDOS trial (NCT02368886). Initially, a daily dose of 160 mg for 3 weeks followed by a 1-week break was the standard approach to treatment with regorafenib, but the trial looked at a dose-escalation method of starting at 80 mg of the drug given daily with a weekly escalation of 40 mg until reaching 160 mg.

The randomized, multicenter, open-label study looked at 116 patients randomly assigned to either a dose-escalation group (n = 54) or standard-dose group (n = 62). Forty-three percent (95% CI, 29%-56%) of patients in the dose-escalation group met the primary end point of initiating their 3rd cycle of treatment without stopping compared with 26% (95% CI, 15%-37%) in the standard-dose group (P = .043). This demonstrated the benefits of a personalized approach to treatment with regorafenib focusing on treatment duration rather than intensity, according to Ahn.

TRANSCRIPTION:

0:08 | Regorafenib has been around for several years now, and that [approval] was based off the randomized phase 3 CORRECT trial. Subsequently, there was a Japanese study called RadioCORRECT, which showed an improvement in OS and PFS in patients with treatment-refractory metastatic CRC irrespective of the genomic mutation present in their tumor.

0:28 | A lot has changed in terms of how we prescribe regorafenib. In the past, the recommendations were to give it at a full dose of 160 mg daily for 3 weeks on followed by a 1-week break. But based off the more recent randomized phase 2 trial from the ReDOS trial, led by Dr. Tanios S. Bekaii-Saab, we know that the appropriate treatment strategy for using regorafenib is in a dose-escalation fashion where the study showed that it's more about...the duration rather than dose intensity. And when we see patients who receive regorafenib based off their dose tolerability, [they] have actually a better median OS compared to what was initially projected on the CORRECT trial.