Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

3529 Background: PTK/ZK is an oral, antiangiogenic inhibitor of tyrosine kinase signaling of all known vascular endothelial growth factor receptors (VEGFR). PTK/ZK in combination with FOLFOX4 has been investigated in first line (CONFIRM 1[C1]) and second line (CONFIRM 2 [C2]) mCRC pts. METHODS: In both trials, pts were randomized to receive PTK/ZK or placebo. Since high LDH and poor performance status (PS) have been shown to indicate poor prognosis in mCRC, pts were stratified by baseline serum LDH (≤ or > 1.5 X ULN) and PS (0, 1-2), yielding 4 strata per trial. Exploratory analysis of the high LDH strata in C1 indicated that these pts may derive the most benefit from PTK/ZK treatment. The purpose of this pre-planned meta-analysis of C1 and C2 is to determine whether the treatment effect of C1 and C2 are consistent. RESULTS: Both trials showed strikingly similar results. High LDH pts comprise approximately 30% of the total pt population. PTK/ZK seems to have the same strong effect on PFS in high LDH pts in both 1st and 2nd line mCRC with a HR for PFS of 0.67 (p =0.010) for C1 and 0.63 (p < 0.001) for C2 (N=250 and N=316, respectively). The safety profile of PTK/ZK was highly consistent. The most frequent grade 3/4 AEs attributable to PTK/ZK were hypertension, diarrhea, fatigue, nausea, vomiting and dizziness. Increases in AEs associated with antiangiogenic therapy such as bowel perforations and bleeding complications were not observed in the PTK/ZK arms of both trials. In the meta-analysis, PTK/ZK effect on PFS is moderate in the overall population (HR 0.85, p-value 0.005). In contrast, the effect on PFS is strong and clinically meaningful in the high LDH population (HR 0.65, p-value < 0.001, N=566). CONCLUSION: This meta-analysis is the largest study of poor prognosis pts with high serum LDH in metastatic colorectal cancer. These data suggest that PTK/ZK significantly improves PFS in high LDH pts. Further evaluation of PTK/ZK in this pt population is planned. [Table: see text].


Journal article


J Clin Oncol

Publication Date