P-262 - The impact of variations in KRAS codon 12 and 13 point mutation on the efficacy of cytotoxic chemotherapy for metastatic colorectal cancer (CRC)

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anti-Cancer Agents & Biologic Therapy
Biomarkers
Colon Cancer
Rectal Cancer
Presenter I. Nakayama
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors I. Nakayama1, E. Shinozaki2, M. Suenaga3, M. Ogura3, M. Ozaka3, T. Wakatsuki4, N. Mizunuma3
  • 1Cancer Institute Hospital, Koto-ku/JP
  • 2Cancer Institute Hospital of JFCR, Koto-ku/JP
  • 3Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto-ku/JP
  • 4Cancer Institute Hospital Department of gastroenterology, Koto-ku/JP

Abstract

Introduction

Different mutant amino acids in the KRAS of codon 12 and 13 were reported to have different tumor aggressiveness in human tumor cells. However it is not clarified whether there are differences in the efficacy of cytotoxic chemotherapy among KRAS mutation variants.

Methods

Of the 1869 consecutive CRC patients analyzed KRAS codon12 and 13 mutational status in our institute between Nov 2006 and Dec 2013, 107 KRAS mutant patients were received systemic chemotherapy for the metastatic CRC as 1st line treatment. Previous chemotherapy including oxaliplatin and irinotecan as NAC setting or adjuvant within 6 months were excluded. Overall survival (OS), Progression-free Survival (PFS) and Objective Response Rate (ORR) were assessed according to KRAS mutational sub-types (G12D, G12V and G13D).

Results

Baseline characteristics were as follows (N = 107): median age (range), 64 (32-76); male/female, 58/49;ECOG PS 0-1/2/unknown, 92/1/14; KRAS mutation sub-type G12D/G12V/G13D/others, 43(40%)/28(26%)/21(20%)/15(14%); right-sided colon (Cecum to Transverse colon) /left-sided colorectal (Descending colon to anal canal)/double or triple cancer/unknown, 45/47/2/13. Oxaliplatin-containing regimen was chosen in more than 95% of the all cases. In about 75% of all cases, bevacizumab was used with cytotoxic agents. No one was not administered anti-EGFR antibody as initial treatment. Median follow-up was 20.3 months at cut-off data. Median OS and PFS were as follows: 34.2 and 14.6 months (all), 50.8 and 17.5 months (G12D), 32.1 and 13.0 months (G12V) and 25.4 and 11.2 months (G13D). ORRs were 48.9% (all), 46.9% (G12D), 46.2% (G12V) and 47.1% (G13D) respectively. There were no statistically significant differences in all these therapeutic endpoints (OS, PFS and ORR) among KRAS mutation sub-types.

Conclusion

The variations of KRAS mutation on codon 12 and 13 (G12D, G12V and G13D) could not affect the efficacy of cytotoxic chemotherapy for metastatic CRC.

Figure: P-262