- Design
- Randomised phase 2 trial, closed early for poor accrual and funding
- Population
- 22 patients with refractory RAS wild-type metastatic colorectal cancer
- Primary outcome
- Overall survival
- Effect
- Median 21.9 vs 13.3 months (regorafenib first vs anti-EGFR first), one-sided P=0.114
REVERCE II was a randomised phase 2 trial in RAS wild-type metastatic colorectal cancer previously treated with fluoropyrimidine, oxaliplatin and irinotecan. Patients received regorafenib followed by anti-EGFR therapy (with or without irinotecan), or the reverse order. The primary endpoint was overall survival. The trial closed early because of slow enrolment and lack of funding, with only 22 patients (12 and 10).
Sequential treatment was started in 33% (4 of 12) of the regorafenib-first arm and 80% (8 of 10) of the anti-EGFR-first arm. Median overall survival was 21.9 vs 13.3 months (one-sided P=0.114), which did not meet significance. Progression-free survival on the first treatment was 2.5 vs 5.6 months, and progression-free survival on the second was 3.7 vs 2.0 months. Sequential progression-free survival was 9.3 vs 9.6 months. No significant differences in adverse effects were seen.
The authors suggest regorafenib first may carry a survival benefit, but with 22 patients, and a minority completing the sequence in one arm, the result is a hypothesis and not a basis for changing practice.
- Do not change the sequence of therapy on the basis of this trial.
- Twenty-two patients cannot support conclusions on survival differences.
- Only 4 of 12 patients in the regorafenib-first arm received the second therapy.
- Anti-EGFR therapy remains an option in RAS wild-type disease per existing guidance.
Why it matters
Sequencing questions in refractory colorectal cancer are common and rarely have randomised answers.
Don't overread it
A trial closed early with 22 patients is underpowered and inconclusive.
The statistics, in plain English
A one-sided P of 0.114 for survival is not significant, and with 22 patients, large survival differences can arise by chance. Progression-free survival on first treatment favoured the other arm, which shows how mixed the signals were.
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