Updated CONCUR Trial Data: Regorafenib Monotherapy in Asian Patients with Metastatic Colorectal Cancer
The oral multikinase inhibitor regorafenib has demonstrated significant improvements in overall survival (OS) in previously treated patients with metastatic colorectal cancer (mCRC) whose disease has failed to respond to standard therapies. The randomized, placebo-controlled, phase 3 CONCUR trial evaluated the efficacy and safety of regorafenib in Asian patients with mCRC. In this trial, patients with mCRC whose disease progressed within <3 months after completing ?2 previous standard therapies, including fluoropyrimidine-, oxaliplatin plus irinotecan-based chemotherapy, an anti-VEGF therapy, and an anti-EGFR therapy if the patient had KRAS wild-type disease, were randomized in a 2:1 ratio to receive regorafenib 160 mg or placebo, daily. At ESMO 2014, Kim and colleagues reported the updated OS data, as well as the results of a planned subgroup analysis of OS outcomes by previous targeted therapy (Kim et al. CONCUR trial. ESMO 2014: Abstract 5000).
Of the 204 randomized patients in the CONCUR trial, 41% had not received previous anti-VEGF or anti-EGFR therapy. The OS analysis in the overall patient population showed that regorafenib therapy was associated with a 45% reduction in mortality risk compared with placebo (median OS, 8.8 vs 6.3 months; hazard ratio (HR), 0.55; P = .0002). Regorafenib also resulted in a significant improvement in progression-free survival (PFS), reducing the risk for disease progression by 69% (HR, 0.311; P <.0001), and led to a disease control rate of 52% versus 7% with placebo.
A subgroup analysis by previous targeted therapy showed that the patients with no previous targeted therapies derived the most benefit in OS from regorafenib therapy, with a median OS that was nearly doubled compared with placebo (9.7 vs 4.9 months; HR, 0.31). The benefit obtained by the subgroup of patients who received previous targeted therapy was smaller, with a median OS of 7.4 months versus 6.7 months with placebo (HR, 0.78). Furthermore, there was no benefit in the anti-VEGF only subgroup, likely as a result of an imbalance in the posttreatment group. An exploratory post-hoc analysis of OS after censoring at the start of the posttreatment study showed an even greater OS benefit (HR, 0.41) than reported in the intent-to-treat population. In terms of toxicity, common treatment-emergent grade 3 or 4 adverse events associated with regorafenib therapy were hand-foot skin reaction (16%), hypertension (12%), and hyperbilirubinemia (12%).
Kim and colleagues concluded that regorafenib therapy provided a significant improvement in OS in Asian patients with mCRC whose disease progressed after standard therapies, with a particular benefit in patients who had not received previous targeted therapy; the safety profile was consistent with that seen in previous analyses.