Optimizing Regorafenib Dosing in Refractory Colorectal Cancer: REARRANGE Trial

At the ESMO World Congress on Gastrointestinal Cancer 2019 held in Barcelona, Dr. G. Argiles presented the results of the REARRANGE Phase 2 clinical trial. This study evaluated whether alternative dosing strategies for Regorafenib (Stivarga), a multikinase inhibitor, could improve tolerability for patients with refractory metastatic colorectal cancer (mCRC).

Study Design: REARRANGE Trial

The trial randomized 299 patients with refractory mCRC in a 1:1:1 ratio to receive three different dosing schedules (28-day cycles):

1. Standard Dose Group: 160 mg once daily (3 weeks on / 1 week off).
2. Reduced Dose Group: 120 mg once daily (3 weeks on / 1 week off).
3. Intermittent Dose Group: 160 mg once daily (1 week on / 1 week off).

The primary endpoint was the incidence of Grade 3 or 4 adverse events.

Key Findings

The trial did not meet its primary endpoint of a 20% reduction in Grade 3/4 side effects with the alternative schedules:

• Grade 3/4 Side Effect Incidence:
  • Standard Dose: 60%
  • Reduced Dose: 54%
  • Intermittent Dose: 55%

However, both alternative groups showed numerically lower rates of certain specific toxicities, such as fatigue, asthenia (muscle weakness), and proteinuria.

Efficacy Comparison

Importantly, the efficacy remained consistent across all three groups, showing that flexible dosing does not necessarily mean reduced benefit:

• Median Overall Survival (OS):
  • Standard Dose: 7.4 months
  • Reduced Dose: 8.6 months
  • Intermittent Dose: 7.1 months
• Median Progression-Free Survival (PFS): Approximately 2.0 months for all groups.

Conclusion

The REARRANGE trial confirms that flexible Regorafenib dosing strategies (such as starting at a lower dose or using an intermittent schedule) are feasible and achieve similar survival outcomes to the standard 160 mg dose with potentially better management of specific side effects. This provides clinicians and patients with more options to tailor treatment to individual tolerance levels.

Source: ESMO World GI 2019 Press Release - REARRANGE Trial Results

#ColorectalCancer #Regorafenib #Stivarga #REARRANGETrial #CancerTreatment #DoseOptimization

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