ESMO 2014: Phase III Study Confirms Regorafenib’s Survival Benefit in Metastatic Colorectal Cancer


Key Points

  • In Asian patients with previously treated colorectal cancer, single-agent regorafenib improved median overall survival from 6.3 months in the placebo arm to 8.8 months, a 45% reduction in death.
  • In patients without prior treatment with a targeted agent, median overall survival was 9.7 months vs 4.9 months, respectively (HR = 0.31).
  • When censored at the time of starting subsequent postprogression therapy, patients without prior targeted therapy had a median overall survival of 10.6 months with regorafenib vs 4.8 months with placebo (HR = 0.27).

The phase III CONCUR trial of regorafenib (Stivarga) monotherapy in Asian patients with previously treated metastatic colorectal cancer confirmed the overall survival benefit seen in the previous CORRECT trial and in an exploratory analysis suggested 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 Songpa-gu, Korea. Dr. Kim presented the findings at the 2014 ESMO Congress in Madrid (Abstract 500O)


The multicenter study randomly assigned 136 Asian patients to regorafenib 160 mg daily and 68 to placebo. 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 death (P = .0002). In the CORRECT trial, median overall survival was 6.4 months and 5.0 months, respectively (hazard ratio [HR] = 0.77; P = .0002). While approximately 40% of CONCUR patients received previous targeted therapy, in the CORRECT trial 100% had received previous anti-VEGF agents and 43% had received anti-EGFR therapy.

In the 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 who had received these drugs.

Exploratory Analysis

“The subgroup analysis of overall survival by prior targeted therapy generally favored regorafenib, but may have been impacted by imbalances in post-study anticancer treatments,” Dr. Kim noted. Such treatments were received by 31% of the regorafenib group compared to 48% 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 to be 8.8 months in the regorafenib arm and 4.8 months in the placebo arm (HR = 0.41), and for patients without prior targeted therapy (n = 82) it was 10.6 months vs 4.8 months, respectively (HR = 0.27).

“The exploratory post-hoc analysis of overall survival with censoring at the start of post-study 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 sample size of this exploratory analysis was small and these results should be interpreted with caution.

Adverse events in CONCUR were consistent with the known safety profile of regorafenib in metastatic colorectal cancer. Fourteen percent of patients in the regorafenib group and 6% in the placebo group discontinued treatment due to adverse events.

Dr. Kim reported serving on the advisory board for Merck and Abbvie and receiving research funding from Bayer. For full disclosures of the study authors, visit

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