Treatment with regorafenib significantly improved overall survival (OS) and progression-free survival (PFS) in an Asian population of patients with previously treated metastatic colorectal cancer (mCRC), according to results from the phase III CONCUR trialÂ presented at the ESMO 16th World Congress on Gastrointestinal Cancer.
During his presentation, study author Jin Li, MD, PhD, from the Fudan University Shanghai Cancer Center, Shanghai, China, noted that regorafenib is the first small molecule multikinase inhibitor to demonstrate a survival benefit in patients with mCRC who progressed following standard therapy.Â
Results from the 204 patient CONCUR trial confirm the safety and efficacy of regorafenib that was demonstrated in the pivotal phase III CORRECT trial. The rationale to conduct theÂ CONCUR trial in a more diverse population of patients of Asian descent with mCRC was derived from a subpopulation of the CORRECT trial that included 15% of patients who were of Asian descent (mostly Japanese).
CONCUR was a randomized, double-blind, placebo-controlled phase III study that enrolled patients with mCRC from 25 centers in mainland China, Hong Kong, Taiwan, Republic of Korea, and Vietnam.Â Patients with stage IV adenocarcinoma of the colon or rectum who experienced disease progression within 3 months of completing standard treatment were eligible. Patients must have undergone a minimum of two prior treatment lines of fluoropyrimidine, oxaliplatin, or irinotecan; previous anti-VEGF and anti-EGFR treatments were allowed, but not required for eligibility.Â
Patients were stratified by metastatic site (single vs multiple) and by time from diagnosis of metastatic disease to randomization (<18 months vs â‰¥18 months) and randomized 2:1 to receive regorafenib at 160 mg daily during the first 3 weeks of each 4-week cycle plus best supportive care (BSC) or placebo plus BSC until disease progression, unacceptable toxicity, or withdrawal of consent.
The trial’s primary endpoint was OS, and secondary endpoints were PFS, tumor response, disease control rate (DCR) and safety. Reported P
-values are one-sided.
Regorafenib was administered to 136 patients, and 68 patients received placebo; patient demographics and baseline characteristics were well balanced between these arms. Median patient age was 57 years. ECOG PS 1 was recorded in 75% of patients, and PS 0 was recorded in 25% of patients. Anti-EGFR or anti-VEGF therapies had not been previously received by 41% of patients, and the majority (75%) of patients had received three or more treatments for mCRC.
Significantly improved OS and PFS were demonstrated with regorafenib over placebo. Median OS was 8.8 months and 6.3 months in the regorafenib and placebo arms, respectively (hazard ratio [HR] = 0.550; 95% CI: 0.395-0.765; P
PFS was improved to a median of 3.2 months with regorafenib compared with 1.7 months with placebo (HR = 0.311; 95% CI: 0.222-0.435; P
<.0001). The DCR also favored regorafenib over placebo with 52% and 7%, respectively.
The most commonly reported grade 3 or 4 treatment-related adverse events with regorafenib were hand-foot skin reaction, hypertension, and hyperbilirubinemia, which were reported by 16%, 12%, and 12% of patients in the regorafenib arm, respectively. The occurrence of hand-foot skin reaction and hypertension are consistent with other reports of regorafenib in patients of Asian descent.
Li J, Qin S, Yau T, et al. CONCUR: aÂ randomized, double blind, placebo-controlled phase 3 study of regorafenib monotherapy in Asian patient with previously treated metastatic colorectal cancer.Â Presented at: 16th World Congress on Gastrointestinal Cancer; June 25-28, 2014; Barcelona, Spain. Abstract O-0023
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