MPI abstract published on the ESMO homepage shows that the MPI's genetic response profile can predict efficacy of adjuvant 5-FU in colon cancer

2014-09-17

Hoersholm; September 17, 2014 - Medical Prognosis Institute A/S (MPI) announced today that those colon cancer patients that were predicted sensitive to 5-FU by MPI's genetic response profile had half the risk of dying of their cancer compared to those that were predicted not-sensitive. The data are from a study with more than 600 patients who all received 5-FU chemotherapy after surgery for colon cancer.  The  data have been published on the ESMO (European Society for Medical Oncology) home page as an abstract with the title "A genetic response profile to predict efficacy of adjuvant 5-FU in colon cancer" and will be discussed on Saturday 27th September with experts on the ESMO Conference . 
There is a huge medical need for knowing which individual patient is likely to respond to 5-FU. 5-FU and 5-FU analogues are used to treat millions of patients with different forms of cancer yearly.
The abstract concludes that "Our data could suggest that the present 5-FU signature provides independent predictive information regarding benefit from adjuvant 5-FU in Colon Cancer patients
 
"I'm very excited that MPI's strong technology again has been verified. Until now there has been no useful biomarker for 5-FU efficacy to guide patient treatment. The data show that patients who are not sensitive to treatment with 5-FU have a double risk of dying. I believe that the ability to see the differences in patient's response to drugs can significantly help us find and develop better cancer treatments.  5-FU is used in millions of patients annually and prediction of who will benefit and who will not - can solve a huge medical need"; Said CEO, Peter Buhl Jensen
 
Abstract published on the ESMO homepage (please also see below)
 
Data will be presented and discussed with experts at the annual ESMO conference in Madrid on September 27, 2014, from 1pm-2pm in room 'Granada' in a Poster Discussion Session.

----------------------------------------------------------------
Abstract: A genetic response profile to predict efficacy of adjuvant 5-FU in colon cancer
Background: There is a clinical need for biomarkers of response to adjuvant 5-fluorouracil (5-FU) in colon cancer (CC). The current project seeks to validate a predictive 5-FU gene expression profile. A similar model has recently been validated with MD Anderson in three different clinical settings [1] and with researchers from AstraZeneca with fulvestrant [2]. Methods: The 5-FU profile consisted of in total 205 positively and negatively correlated genes mapped to 669 probe sets (on the ALMAC Colon DSA). This profile was tested using  expression data obtained from a Colon DSA gene expression array from ALMAC  applied on the   PETACC-3 CC population [3] with formalin fixed paraffin embedded (FFPE) tissue from 636 stage III CC patients treated adjuvantly with 5-FU with or without irinotecan. It was also tested on ALMAC Colon DSA data obtained from FFPE tissue from 359 stage II CC patients who did not receive adjuvant treatment [4]. The analyses were performed using Cox proportional hazards (CPH) regression models and Kaplan-Meier curves. The logrank test was used to compare the survival distributions. Results: In the PETACC-3 cohort the 5-FU predictive profile showed a statistically significant association with overall survival (OS) (hazard ratio (HR) = 0.47 (0.34, 0.63), P = 7.4e-07; binary scores). In the untreated cohort no differences were observed in OS (HR = 0.96 (0.67, 1.4), P = 0.849; binary scores). The statistical significance of the effect of the profile score (as continuous variable) adjusted for several relevant clinicopathological parameters including microsatellite instability (MSI) vs stability (MSS) and KRAS mutation status was confirmed in a multivariable CPH model on the PETACC-3 data (Table). Conclusions: Our data could suggest that the present 5-FU signature provides independent predictive information regarding benefit from adjuvant 5-FU in CC patients.

PETACC-3
HR estimates, variables with P < 0.05
HR CI
5FU predict 1 unit = 1 iqr 0.69 0.58, 0.82
T stage T4 vs T3 2.03 1.4, 2.95
N stage N2 vs N1 2.01 1.45, 2.79
grade G34 vs G12 1.81 1.07, 3.07
KRAS mut vs wt 1.89 1.34, 2.67
MSI, MSI vs MSS 0.42 0.21, 0.81
 
[1] JNCI 2013;105:1284-1291
[2] PLoS One 2014;9:e87415
[3] JCO 2009;27:3117-3125
[4] JCO 2011;29:4620-4626
----------------------------------------------------------------
 
 
About MPI's genetic response profile called Drug Response Predictor - DRP
MPI's lead product DRP is a tool to develop tumor-derived gene signatures that may predict which cancer patients are high likely responders to a given anticancer product. The DRP has been tested in 26 trials where 22 trials showed that the DRP could predict which patients had a positive effect of the treatment. The DRP has also been externally validated and published in collaboration with leading statisticians at the MD Anderson Cancer Center. The DRP method can be used to design the Clinical Development Plan i.e. to select which indications are relevant for a given anticancer drug. Further to and in addition to this, individual patient's gene patterns can be analyzed as part of a screening procedure for a clinical trial to ensure inclusion of patients who have a high likelihood of response to the drug. The DRP method can be used in all cancer types and has been patented for more than 60 anticancer drugs in the US in 2013.
 
For further information please contact
CEO Peter Buhl Jensen, Professor, MD, PhD
E-mail: pbj@medical-prognosis.com
Cell Phone: (+45) 21 60 89 22

Certified Advisor: Carsten Yde Hemme, PricewaterhouseCoopers, Strandvejen 44, 2900 Hellerup, Denmark