In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e15029-e15029
Abstract:
e15029 Background: Initially unresectable colorectal liver metastases can become resectable after chemotherapy. Chemotherapy combined with EGF-receptor antibodies has shown consistent high response rates in patients with RAS wildtype tumors. However, the influence of RAS mutations other than exon 2 mutations in the context of a conversion strategy has not been systematically studied yet. Methods: Out of a cohort of 424 patients with mCRC, we identified 30 patients with initially unresectable KRAS exon 2 wildtype colorectal liver metastases who received neoadjuvant chemotherapy including cetuximab or panitumumab between January 2008 and February 2014. In all patients extended RAS analysis (KRAS and NRAS exon 3 codon 59 and 61 and exon 4 codon 117 and 146) was carried out. Resection status (R0, R1 or R2), PFS and OS were recorded in all patients and maximum tumor shrinkage was calculated. Results: RAS mutation analysis identified further KRAS mutations in 4/30 patients (13.3%). No NRAS mutations were found. In none of these four patients a R0 resection could be achieved. In contrast, 15/26 (57.7%) RAS wildtype patients could be R0 resected. Median survival of patients with a RAS wildtype tumor was 64.0 [range: 7.4-98.6] months vs. 28.0 [range: 16.4- 40.6] months in those with a RAS mutation (hazard ratio, HR, 0.53; 95% confidence interval, CI: 0.15-1.81, p = 0.3). Median PFS in patients with a RAS mutation was 8 [range: 6-28.8] months compared to 10.4 [range, 1.7-15.2] months in patients with a RAS wildtype cancer. Median overall survival was 〉 63.3 months in R0-resected patients vs. 30.0 months in those with a R1 or R2 resection (HR 0.23; [95% CI 0.10- 0.75; p = 0.008). Conclusions: Our data suggest that a RAS wildtype status and a R0 resection are the strongest predictors for overall survival. The extended RAS analysis allows a better patient selection for anti-EGFRbased conversion chemotherapy before secondary resection of colorectal liver metastases.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.15_suppl.e15029
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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