Regorafenib improves survival in patients with metastatic CRC progressing after standard therapy, especially in those without prior targeted therapies

The phase III CONCUR trial previously demonstrated that regorafenib improves survival in patients with metastatic colorectal cancer (mCRC) who progressed after standard therapy. During ESMO 2014, results of a preplanned subgroup analysis of this study evaluating the overall survival (OS) by prior targeted therapy were presented. The outcome indicated that the OS benefit was greater in patients who did not receive prior anti-VEGF or anti-EGFR therapy.

After the CORRECT trial, CONCUR was the second phase III study showing that regorafenib (REG) improves OS in patients with mCRC who progress after standard therapy. In fact, the CONCUR study demonstrated a 45% reduction in the risk of death for patients treated with regorafenib compared with placebo, while CORRECT demonstrated a hazard ratio of 0.77 in favor of regorafenib.

In the CONCUR study, a total of 204 patients with mCRC who progressed less than 3 months after completing standard therapy, were randomized (2:1) to regorafenib 160 mg daily or placebo during the first 3 weeks of each 4-week cycle. Patients had 2 or more prior standard treatments for mCRC, including fluoropyrimidine, oxaliplatin and irinotecan. Prior anti-VEGF or anti-EGFR targeted therapy was allowed, but not mandatory. The primary endpoint of the study was OS, while secondary endpoints included progression-free survival (PFS), response, disease control rate (DCR) and safety.

The median OS was 8.8 months with regorafenib compared to 6.3 months with placebo (HR[95%CI]: 0.55 [0.40-0.77]; p = 0.0002). In addition to this, regorafenib improved the progression-free survival (PFS) (3,2 months vs 1,7 months with placebo; HR[95%CI]: 0.311 [0.222–0.435]; p < 0.0001) and the disease control rate compared to placebo (52% vs.7%). The most frequent treatment-emergent adverse events grade ≥ 3 with REG were hand-foot skin reaction (16%), hypertension (12%) and hyperbilirubinemia (12%).

In total, 41.2% of the regorafenib treated patients did not receive prior targeted (anti-EGFR or anti-VEGF) therapy, compared to 38.2% in the placebo arm. In the regorafenib arm, 23.3%, respectively 17.6% and 17.6% of patients received prior anti-VEGF, anti-EGFR or both. Looking at the OS in function of prior therapy, patients who received no prior targeted therapy seemed to derive more benefit from regorafenib. In fact, the median OS for patients without prior targeted therapy was 9.7 months with regorafenib, compared to 4.9 months with placebo (HR[95%CI]: 0.31 [0.19-0.53]). In patients who had received prior anti-VEGF and/or anti-EGFR therapy, regorafenib was associated with an OS of 7.4 months compared to 6.7 months with placebo (HR[95%CI]: 0.78 [0.51-1.19]). An overview of OS data in function of the type of prior targeted therapy is depicted in the section ‘slides’ related to this abstract and these data generally favored regorafenib. Notably, an imbalance in post-progression treatment favored placebo in the anti-VEGF only subgroup. In addition to this, an exploratory post-hoc analysis of the OS 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.


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). Presented at ESMO 2014; Abstract 500O.

Speaker Tae Won Kim


Prof. Tae Won Kim, MD,
Asian Medical Center, Seoul, Korea


See: Keyslides

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