1654P - Quantitative measurement of KRAS mutated alleles in plasma as prognostic marker in metastatic KRAS mutant colorectal cancer

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Biomarkers
Colon Cancer
Rectal Cancer
Presenter Karen-Lise Spindler
Authors K.G. Spindler1, N. Pallisgaard2, R. Andersen2, A. Jakobsen3
  • 1Oncology, University of Southern Denmark, 7100 - Vejle/DK
  • 2Department Of Clinical Biochemistry, Vejle Hospital Sygehus Lillebaelt, Vejle Sygehus, Vejle, DENMARK, 7100 - Vejle/DK
  • 3Oncology, Vejle Hospital Sygehus Lillebaelt, Vejle Sygehus, 7100 - Vejle/DK

Abstract

Purpose

We investigated the prognostic value of quantitative measures of KRAS mutated alleles (pKRAS) in plasma from patients with metastatic colorectal cancer (mCRC) prior to treatment with pemetrexed and gemcitabine in a phase II clinical trial.

Methods

Inclusion criteria comprised; histopathologically verified mCRC with KRAS mutant chemotherapy resistant disease, indication for third-line chemotherapy, adequate organ function and performance status. Patients received pemetrexed (initially 500 mg/m2 q3w) combined with Gemcitabine (1250 mg/m2 day 1 and 8) until progression or unacceptable toxicity. RECIST version 1.1, NCI-CTCAE version 4.0 and Kaplan-Meier statistics were used for evaluation of endpoint measures. Plasma was obtained from a pre-treatment EDTA blood-sample, and the number of pKRAS alleles was assessed by an in-house quantitative polymerase chain reaction.

Results

Forty patients were included during April 2010-Aug 2011. The median number of cycles was 3 (range 0-12). Thirty-six percent of patients obtained disease stabilisation, but no objective responses were observed. The median PFS and OS were 2.8 (range 2.1-4.0) and 5.4 (range 4.3-7.0) months (mo), respectively. Pre-treatment blood samples and archival tumor tissue were available for analysis in all patients. Thirty-three mutations were detectable in the peripheral blood, whereas 7 patients had primary tumor mutations and wildtype status according to the blood sample. The median level of pKRAS alleles was 900 alleles/ml. When divided into quartiles of pKRAS, significantly shorter PFS and OS were revealed with increasing levels of alleles. The median PFS was 2.1 mo (95%CI 1.9-2.1) in patients with high levels (> median) compared to 4.2 mo (95%CI 2.5-5.1) in those with lower levels (< median) (HR = 3.0, p = 0.0002), and the OS 4.1 (95%CI 3.0-5.2) and 8.0 (95%CI 5.1-9.6) mo, respectively (HR = 3.0, p = 0.0005).

Conclusion

A high pre-treatment level of pKRAS alleles had a detrimental effect on both PFS and OS, whereas low levels were correlated to a better chance of disease stabilisation. This confirms our data from two previous study cohorts and pKRAS could therefore serve as a new prognostic marker in KRAS mutant mCRC.

Disclosure

All authors have declared no conflicts of interest.