Colorectal cancer: gradual dose escalation improves regorafenib safety

  • Lancet Oncol

  • curated by Jim Kling
  • Univadis Clinical Summaries
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Takeaway

  • Starting regorafenib at a dose of 80 mg/day, with weekly 40 mg escalation to reach 160 mg/day, was similarly effective and less toxic than the standard dosing strategy (160 mg/day) in refractory metastatic colorectal cancer.

Why this matters

  • Various dosing regimens are used to reduce the fatigue and hand-foot skin reaction that often accompany regorafenib use, but none are supported by clinical evidence.

Study design

  • Open-label, multicenter, phase 2 study (ReDOS; n=116).
  • Patients were randomly assigned 1:1:1:1 to standard dose or dose escalation, plus preemptive or reactive clobetasol use.
  • Funding: Bayer HealthCare Pharmaceuticals.

Key results

  • The researchers combined the preemptive and reactive groups because of the absence of a significant interaction (P=.74).
  • OS was better in the escalation group, although the result did not reach statistical significance (aHR, 0.742; P=.18).
  • More subjects in the dose escalation group initiated cycle 3 (43% vs 26%; 1-sided P=.043).
  • The most common grade 3-4 adverse events included fatigue (13% dose escalation vs 18% in the standard dose group), hand-foot skin reaction (15% vs 16%), abdominal pain (17% vs 6%), and hypertension (7% vs 15%).

Limitations

  • Small sample size.