598P - Cetuximab plus mFOLFOX-6 as first-line therapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases: An open, non-rand...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Biomarkers
Colon Cancer
Rectal Cancer
Presenter sanjun Cai
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors S. Cai1, W. Zhang2, W. Li3, Y. Xu4, W. Gu3, Z. Guan1, J. Cai5, C. Song6, J. Xu7, P. Chi8, J. Lin9, K. Zhang10, D. Li11, X. Wang12, H. Pei13, X. Zhang14, D. Wan15, J. Wang16, C. Dang17, X. Yuan18
  • 1Colorectal Surgery, Fudan University Shanghai Cancer Center, 200032 - Shanghai/CN
  • 2Medical Oncolgy, Fudan University Shanghai Cancer Centre, Shanghai, P.R. China, 200032 - shanghai/CN
  • 3Department Of Medical Oncology, Fudan University Shanghai Cancer Center, 200032 - Shanghai/CN
  • 4Colorectal Surgery, Fudan University Shanghai Cancer Centre, Shanghai, P.R. China, 200032 - shanghai/CN
  • 5Abdominal Surgery, Cancer Hospital&Institute Chinese Academy of Medical Sciences Peking Union Medical College, 100010 - beijing/CN
  • 6Colorectal Surgery, Liaoning Cancer Hospital, 110042 - shenyang/CN
  • 7Department Of General Surgery, Zhongshan Hospital Fudan University, 200032 - Shanghai/CN
  • 8Colorectal Surgery, Fu jian medical university Union hospital, 350001 - fuzhou/CN
  • 9Colorectal Surgery, 1nd Affiliated Hospital of ZHEJIANG University, NA - hangzhou/CN
  • 10Colorectal Cancer, Hubei cancer hospital, 430079 - wuhan/CN
  • 11Colorectal Surgery, Zhejiang cancer hospital, 310022 - hangzhou/CN
  • 12Colorectal Surgery, 2nd Affiliated Hospital of Harbin Medical University, NA - haerbin/CN
  • 13Colorectal Surgery, Xiangya hospital –Center south university, 410008 - changsha/CN
  • 14Colorectal Surgery, 1nd Affiliated Hospital of ZHENGZHOU University, NA - zhengzhou/CN
  • 15Colorectal Department, Sun Yat-Sen University Cancer Center, 510060 - Guangzhou/CN
  • 16Colorectal Cancer, 6nd Affiliated Hospital of Sun Yat-sen University, 510655 - guangzhou/CN
  • 17Surgical Oncology, First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, 710061 - xian/CN
  • 18Colorectal Cancer, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science & Technology, 432600 - wuhan/CN

Abstract

Aim

This study aims to observe whether the addition of cetuximab(cet) further increases the curative resection rate and improves long-term survival for patients(pts) with KRAS wide-type unresectable colorectal liver limited metastases in China.

Methods

Pts were planned to receive cetuximab (500 mg/m2 q2w) plus mFOLFOX-6 including Oxaliplatin 85 mg/m2 plus CF 400 mg/m2 and 5-FU as a 400 mg/m2 bolus followed by 2400 mg/m2 infusion over 46 hours on day 1, repeated every 2 weeks until metastatic leision became resectable or for a maximum of 9 cycles. The primary endpoint was R0 resection rate in intention to treat (ITT) cohort. The second endpoint included objective response rate (ORR), progression-free survival (PFS), over survival (OS) and safety. Per protocol (PP) cohort were defined as pts without major protocol violation and whose tumours were assessed for hepatectomy feasibility by a multidisciplinary team.

Results

Between Dec. 2010 and Nov. 2013, 204 pts were screened from 17 centers in China. 130 (63.7%) pts had KRAS exon 2 wild-type tumors. In the ITT cohort (100 cases), the ORR was 61% (95% CI 50.7%, 70.6%), for PP cohort (71 cases), the ORR was 70.4% (95% CI 58.4%, 80.7%). 39 (39%) pts were technically resectable but 34 pts went through surgical treatment. R0 resections were achieved in 27 cases (27%, 95%CI 18.6%, 36.8%), R0/R1 resection and/or radiofrequency ablation were achieved in 33 cases. The ORRs of resectable (39 cases) and unresectable (61 cases) pts were 74.4%, 52.5%, respectively. The median PFS was 10.6m in ITT cohort (95% CI 6.9, 14.7). 90 pts experienced adverse events, mainly including rash (any Gr 68%, Gr 3/4 5%), neutropenia (43%) and malaise (20%). 7 SAEs were reported and 3 pts died. Two pts died during pre-operative chemotherapy from intestinal obstruction and respiratory/cardiac arrest. The other patient died from leukocyte inhibitory and septic shock, and that a causal relationship of study drug cannot be excluded.

Conclusions

With interim analyses combination therapy comprising cetuximab and mFOLFOX-6 was well tolerated with acceptable ORR, R0 resection rates and PFS.

Disclosure

All authors have declared no conflicts of interest.