Impact of early tumor shrinkage on clinical outcome in wild-type-KRAS colorectal liver metastases treated with cetuximab.
OBJECTIVE
To evaluate the impact of early tumor shrinkage (ETS) on long-term outcome in patients with wild-type Kirsten rat sarcoma viral oncogene homolog (KRAS) unresectable colorectal liver metastases (CLM) receiving cetuximab plus chemotherapy.


METHODS
A total of 138 patients in a randomized controlled trial (70 in armA received cetuximab plus chemotherapy, 68 in armB received chemotherapy alone), as previously reported (Ye et al., 2013) were included into this analysis. The cut-off date updated for overall survival (OS) was June 2014. ETS was defined as a ≥ 20% reduction of the longest diameters of the target lesions compared with baseline at the first evaluation (8 weeks). Outcome measures were progression-free survival (PFS) and OS.


RESULTS
There were 132 patients available for evaluation, and ETS occurred more frequently in armA than that in armB (P = 0.003). ETS was associated with longer OS (armA: 35.7 vs. 19.5 months, P < 0.001; armB 28.7 vs. 18.7 months, P = 0.01) and PFS (armA: 13.4 vs. 4.2 months, P < 0.001; armB 7.0 vs. 4.2 months, P = 0.001) compared with patients with no-ETS. Among patients with ETS, there was a significant difference between armA and armB in PFS (P = 0.03), but not in OS (P = 0.19). All 23 patients who underwent liver surgery achieved ETS. In armA, for patients without liver surgery, patients observed ETS also gained an increased survival benefit over those no-ETS in OS (P = 0.02) and PFS (P < 0.001). ETS was an independent predictor of improved OS (hazard ratio 0.56, P = 0.007).


CONCLUSIONS
ETS may serve as a predictor of favorable outcome in patients with wild-type KRAS CLM receiving cetuximab plus chemotherapy.
Department of Oncological Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Le-chi
LC
Ye
Ye
Y
Wei
De-xiang
DX
Zhu
Tao
T
Chen
Jianmin
J
Xu
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068818:Cetuximab / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000821:virology; D005500:Follow-Up Studies; D006498:Hepatectomy; D006801:Humans; D007708:Kirsten murine sarcoma virus / Q000235:genetics*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary* / Q000821:virology; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab
cetuximab; colorectal liver metastasis; early tumor shrinkage