The phase III CONCUR trial1 of regorafenib (Stivarga) monotherapy in Asian patients with previously treated metastatic colorectal cancer confirmed the overall survival benefit seen in the previous CORRECT trial,2 and in a planned subgroup analysis, suggesting the benefit is substantial in patients not previously treated with a targeted agent.
“CONCUR is the second phase III trial showing that regorafenib improves survival in patients with metastatic colorectal cancer who progress after standard therapies,” said Tae Won Kim, MD, of the University of Ulsan College of Medicine Asan Medical Center in Seoul, Korea. Dr. Kim presented the findings at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid.
CONCUR Trial
The multicenter study randomly assigned 136 Asian patients to regorafenib at 160 mg daily and 68 to placebo; regorafenib or placebo was administered daily at a schedule of 3 weeks on and 1 week off. In a planned subgroup analysis, the CONCUR investigators evaluated overall survival by prior targeted therapy (ie, drugs targeting the vascular endothelial growth factor [VEGF] or the epidermal growth factor receptor [EGFR]).
The study met its primary endpoint, showing that regorafenib improved median overall survival from 6.3 months in the placebo arm to 8.8 months, a 45% reduction in the risk of death compared with placebo (P = .0002). In the CORRECT trial, median overall survival was 5.0 months and 6.4 months, respectively (hazard ratio [HR] = 0.77, P = .0052). While approximately 60% of CONCUR patients received previous targeted therapy, in the CORRECT trial 100% had received previous anti-VEGF agents and 51% had received anti-EGFR therapy.
In the planned subgroup analysis of overall survival by prior targeted therapy, median survival was 9.7 months with regorafenib vs 4.9 months with placebo (HR = 0.31) in patients with no prior targeted therapy and was 7.4 months and 6.7 months, respectively (HR = 0.78) in the subset of those who had received any targeted agent.
Exploratory Analysis
“The subgroup analysis of overall survival by prior targeted therapy generally favored regorafenib but may have been impacted by imbalances in poststudy anticancer treatments,” Dr. Kim noted. Such treatments were received by 31% of the regorafenib group compared to 43% of the placebo group. The investigators, therefore, conducted an exploratory post hoc analysis in which patients (n = 204) were censored at the start of subsequent treatment.
This exploratory analysis found median overall survival for the overall cohort to be 8.8 months in the regorafenib arm and 4.8 months in the placebo arm (HR = 0.41), and for patients who had received no prior targeted therapy (n = 82) it was 10.6 months vs 4.8 months, respectively (HR = 0.27). For patients who had received any prior targeted therapy (n = 122), median overall survival with regorafenib was 7.4 months vs 4.9 months with placebo (HR = 0.57).
“The exploratory post hoc analysis of overall survival with censoring at the start of poststudy treatment favored regorafenib, irrespective of whether or not patients received prior anti-VEGF or prior anti-EGFR therapy,” he said.
Dr. Kim acknowledged that the subgroup sample sizes were small, that censoring in this exploratory analysis could be informative, and, therefore, that these results should be interpreted with caution.
Adverse events in CONCUR were consistent with the known safety profile of regorafenib in metastatic colorectal cancer. Approximately 14% of patients in the regorafenib group and 6% in the placebo group discontinued treatment due to adverse events. ■
Disclosure: Dr. Kim reported serving on advisory boards for Merck and AbbVie and receiving research funding from Bayer. For full disclosures of the study authors, visit www.esmo.org.
References
1. Kim T, Xu R, Yau T, et al: CONCUR: A randomized, placebo-controlled phase 3 study of regorafenib (REG) monotherapy in Asian patients with previously treated metastatic colorectal cancer (mCRC). ESMO 2014 Congress. Abstract 500O. Presented September 27, 2014.
2. Grothey A, Van Cutsem E, Sobrero A, et al: Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): An international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381:303-312, 2013.
