500O - CONCUR: A randomized, placebo-controlled phase 3 study of regorafenib (REG) monotherapy in Asian patients with previously treated metastatic colore...

Date 27 September 2014
Event ESMO 2014
Session Gastrointestinal tumours, colorectal
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Tae Won Kim
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors T.W. Kim1, R. Xu2, T.C.C. Yau3, B. Ma4, H. Pan5, J. Xu6, Y. Bai7, Y. Chi8, L. Wang9, K. Yeh10, F. Bi11, Y. Cheng12, A.T. Le13, J. Lin14, T. Liu15, D. Ma16, J. Shapiro17, J. Kalmus18, S.K. Qin19, J. Li20
  • 1Division Of Hematology/oncology,, University of Ulsan College of Medicine Asan Medical Center, 138-736 - Songpa-gu,/KR
  • 2Department Of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou/CN
  • 3Medical Oncolgy, Queen Mary Hospital University of Hong Kong, Hong Kong/CN
  • 4Medical Oncology, "Prince of Wales Hospital Chinese University of Hong Kong", Hong Kong/CN
  • 5Medical Oncology, "Sir Run Run Shaw Hospital Medical School of Zhejiang University, Hangzhou/CN
  • 6Medical Oncology, Beijing 307 PLA Hospital Cancer Centre, Beijing/CN
  • 7Medical Oncology, The 3rd Affiliated Hospital of Harbin Medical University, Harbin/CN
  • 8Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing/CN
  • 9Medical Oncology, Shanghai First People's Hospital Shanghai Jiaotong University, Shanghai/CN
  • 10Medical Oncology, National Taiwan University Hospital, Taipei/TW
  • 11Medical Oncology, "West China Hospital Sichuan University", Chengdu/CN
  • 12Medical Oncology, Jilin Provincial Tumor Hospital, Changchun/CN
  • 13Medical Oncology, Cho Ray Hospital, Ho Chi Min City/VN
  • 14Colon And Rectum Surgery, Taipei Veteran General Hospital, 11217 - Taipei/TW
  • 15Department Of Oncology, Zhongshan Hospital Fudan University, Shanghai/CN
  • 16Medical Oncology, Guangdong General Hospital, Guangdong/CN
  • 17Global Biostatistics, "Bayer HealthCare Pharmaceuticals ", Whippany/US
  • 18Global Clinical Development, Bayer Pharma AG, Berlin/DE
  • 19Medical Oncology, Cancer Center of Nanjing Bayi Hospital, Nanjing/CN
  • 20Department Of Medical Oncology, Fudan University Shanghai Cancer Center, 200032 - Shanghai/CN

Abstract

Aim

Regorafenib, an oral multi-kinase inhibitor, improves overall survival (OS) in patients with mCRC who progressed after standard therapies. CONCUR (NCT01584830) was designed to evaluate the efficacy and safety of REG in Asian patients with mCRC.

Methods

Patients with mCRC who progressed <3 months after completing standard therapy were randomized (2:1) to REG 160 mg daily or placebo during the first 3 wks of each 4-wk cycle. Patients must have had ≥2 prior standard treatments for mCRC, including a fluoropyrimidine, oxaliplatin, and irinotecan. Prior anti-VEGF or anti-EGFR targeted therapy was allowed, but not mandatory. The primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), response, disease control rate (DCR), and safety.

Results

Demographics and baseline characteristics were balanced in patients randomized to REG (n = 136) or placebo (n = 68). The median age was 57 yrs, all were ECOG PS 0–1, 53% had received >3 treatments for CRC, and 41% had no prior anti-VEGF or anti-EGFR therapy. Treatment with REG resulted in a 45% reduction in the risk of death (median OS 8.8 vs 6.3 months; one-sided p = 0.0002; Table), and improved PFS (HR 0.311; 95%CI 0.222–0.435; one-sided p < 0.0001) and DCR (52% vs 7%). The most frequent treatment-emergent CTCAEs grade ≥3 with REG were hand-foot skin reaction (16%), hypertension (12%), and hyperbilirubinemia (12%). An exploratory subgroup analysis by prior targeted therapy suggests the OS benefit for REG was generally maintained (Table). Notably, an imbalance in post-progression treatment favored placebo in the anti-VEGF only subgroup.

Subgroups by prior targeted therapy N HR (95% CI)
All patients 204 0.550 (0.395–0.765)
No targeted therapy 84 0.359 (0.215–0.601)
Anti-VEGF, or anti-EGFR, or both 120 0.747 (0.488–1.145)
Anti-VEGF only 45 0.987 (0.482–2.025)
Anti-EGFR only 39 0.719 (0.340–1.523)
Both anti-VEGF and anti-EGFR 36 0.484 (0.217–1.081)

Conclusions

Regorafenib provides a statistically significant improvement in OS in Asian patients with mCRC who progressed after standard therapies. Adverse events are consistent with the known safety profile of REG.

Disclosure

T.W. Kim: Member of Pharma Advisory Boards for Merck and Abbvie. Received research funding from Bayer; T.C.C. Yau: Advisory Board member for Bayer; B. Ma: Advisory Board member for Bayer. Received research funding from Novartis, and Merck Serono; J. Shapiro: Employee of Sponsor (Bayer Pharma AG) J. Kalmus: Employee of Sponsor (Bayer Pharma AG); J. Li: Advisory Board member for Roche and Merck. Received research funding from Merck and Amgen. All other authors have declared no conflicts of interest.