Regorafenib (BAY 73-4506) is an oral multikinase inhibitor of a broad range of angiogenic, oncogenic, and stromal kinases. The phase III CORRECT trial was conducted to evaluate efficacy and safety of regorafenib in patients with mCRC who had progressed after all approved standard therapies.Methods
Enrollment criteria included documented mCRC and progression during or ≤3 months after last standard therapy. Patients were randomized 2:1 to receive regorafenib (160 mg od po, 3 weeks on/1 week off) plus BSC, or placebo (PL) plus BSC. Patients continued on treatment until progression, death, or unacceptable toxic effect. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), safety, and quality of life.Results
From May 2010 to March 2011, 760 patients were randomized (regorafenib: 505; PL: 255). Baseline characteristics were balanced between the two arms. Results are available from a pre-planned formal interim analysis. The estimated hazard ratio (HR) for OS was 0.77 (95% CI: 0.64, 0.94; 1-sided P = 0.0052). Median OS was 6.4 months (95% CI: 5.9, 7.3) for regorafenib and 5.0 months (95% CI: 4.4, 5.8) for PL. The estimated HR for PFS was 0.49 (95% CI: 0.42, 0.58; one-sided P < 0.000001). Median PFS was 1.9 months (95% CI: 1.9, 2.1) for regorafenib and 1.7 months (95% CI: 1.7, 1.7) for PL. ORR was 1.0% for regorafenib and 0.4% for PL. DCR (partial response + stable disease) was 44.8% for regorafenib and 15.3% for PL (P < 0.000001). Since the prespecified OS efficacy boundary was crossed (nominal α: 0.0093), the Data Monitoring Committee recommended to unblind the study and patients on PL were allowed to cross over to regorafenib. The most frequent drug-related treatment-emergent grade 3+ AEs in the regorafenib arm were hand-foot skin reaction (16.6%), fatigue (9.6%), diarrhea (7.2%), hypertension (7.2%) and rash/desquamation (5.8%).Conclusions
Statistically significant benefit in OS and PFS was observed for regorafenib over PL in patients with mCRC who have failed all approved standard therapies. No new or unexpected safety signal was found.