545P - Quantitative analyses of early tumor shrinkage on clinical outcome in an open, non-randomized, multicenter phase II clinical trial (CLIME study)

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Colon and Rectal Cancer
Biological Therapy
Presenter Wen Zhang
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors W. Zhang1, S. Cai2, W. Li3, Y. Xu2, W. Gu4, Z. Guan5, P. Chi6, C. Song7, J. Cai8, J. Xu9, J. Lin10, K. Zhang11, D. Li12, X. Wang13, H. Pei14, X. Zhang15, J. Wang16, D. Wan17, C. Dang18, X. Yuan19
  • 1Medical Oncology, Fudan University Shanghai Cancer Centre, 200032 - shanghai/CN
  • 2Colorectal Surgery, 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 Department, Shanghai Cancer Center Fudan University, 200032 - Shanghai/CN
  • 5Colorectal Surgery, Fudan University Shanghai Cancer Center, 200032 - Shanghai/CN
  • 6Colorectal Surgery, Fu jian medical university Union hospital, 350001 - fuzhou/CN
  • 7Colorectal Surgery, liaoning cancer hospital, 110042 - shenyang/CN
  • 8Abdominal Surgery, Cancer Hospital&Institute Chinese Academy of Medical Sciences Peking Union Medical College, 100010 - beijing/CN
  • 9Department Of General Surgery, Zhongshan Hospital Fudan University, 200032 - Shanghai/CN
  • 10Colorectal Surgery, 1nd Affiliated Hospital of ZHEJIANG University, 310003 - hangzhou/CN
  • 11Colorectal Cancer, Hubei cancer hospital, 430079 - wuhan/CN
  • 12Colorectal Surgery, Zhejiang cancer hospital, 310022 - hangzhou/CN
  • 13Colorectal Surgery, 2nd Affiliated Hospital of Harbin Medical University, NA - haerbin/CN
  • 14Colorectal Surgery, Xiangya hospital –Center south university, 410008 - changsha/CN
  • 15Colorectal Surgery, 1nd Affiliated Hospital of ZHENGZHOU University, NA - zhengzhou/CN
  • 16Colorectal Cancer, 6nd Affiliated Hospital of Sun Yat-sen University, :510655 - guangzhou/CN
  • 17Colorectal Department, Sun Yat-Sen University Cancer Center, 510060 - Guangzhou/CN
  • 18Colorectal Surgery, 1st affiliated hospital of xi an jiaotong university, NA - xi an/CN
  • 19Colorectal Cancer, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science & Technology, 432600 - wuhan/CN



Early tumor shrinkage (ETS) is associated with long-term outcome in patients receiving chemotherapy plus cetuximab, which was investigated in CRYSTAL and OPUS trials. CLIME study (NCT01322178) was designed to observe whether the addition of targeted drug in first line further increases the curative resection rate and improves long-term survival in KRAS wide-type colorectal liver limited metastases patients in China. This retrospective analysis aims to show the impact of ETS on long-term outcome in CLIME study.


Radiologic assessments at week 8 were used to calculate the relative change in the sum of the longest diameters of the target lesions. A 20% decrease cutoff value was selected as a dichotomization threshold for further investigation. Outcome measures were objective response rate (ORR), curative resection rate and progression-free survival (PFS). Cox regression models were used to quantify individual changes in tumor size over time and to relate these changes to PFS.


From the ITT cohort (100 cases), 92 patients were available for ETS assessment and 70 pts achieved ETS (76.1%). These data were comparable with quantitative analysis of ETS in CRYSTAL and OPUS trials (table 1). Longer PFS was observed in patients who achieved ETS as compared to patients with no-ETS (10.9m vs. 6.2m, HR 0.203, 95%CI 0.087-0.473, P < 0.0001). In patients who achieved ETS, ORR was much higher than in patients with no ETS (81.4% vs. 13.6%, p < 0.0001). Cetuximab-related AEs (any grade and grade 3/4) seemed to be more common in patients who achieved ETS.

CLIME n = 92 CRYSTAL n = 299 OPUS n = 78
ETS rate (%) 70 (76.1%) 184 (62%) 54 (69%)
mPFS in ETS group 10.9m 14.1m 11.9m
mPFS in no-ETS group 6.2m 7.3m 5.7m
HR 0.203 0.32 0.22
P value <0.0001 <0.001 <0.001

KRAS exon2 wt only


Quantitative analyses from CLIME study further revealed the value of the variable ETS as a potential efficacy outcome measure for KRAS wild-type colorectal liver-limited metastases patient in China. Reference:Piessevaux et al., JCO 2013


All authors have declared no conflicts of interest.