Konference: 2015 51th ASCO Annual Meeting - účast ČR
Kategorie: Gastrointestinální nádory
Téma: Gastrointestinal (Noncolorectal) Cancer
Číslo abstraktu: 4029
Autoři: M.D. Charles S. Fuchs, MPH; Josep Tabernero, MD; MUDr. Jiří Tomášek, Ph.D.; M.D. Ian Chau; prof. MUDr. Bohuslav Melichar, Ph.D.; Prof. Dr. Howard Safran; Mustapha Ali Tehfe; Dr. Filip Dumitru; M.D. Eldar Topuzov, Ph.D.; Dr. Luis (Alberto) Schlittler; Dr. Anghel Adrian Udrea; Dr. William Campbell; Dr. Stephen Brincat; MD Michael Emig; Symantha A. Melemed, Ph.D.; Rebecca R. Hozak; Prof. M.D. David R. Ferry, Ph.D.; William Caldwell; Prof. MD Jaffer A. Ajani
Background: Vascular endothelial growth factors (VEGFs) are key regulators of tumor angiogenesis. RAM, a recombinant human IgG1 monoclonal antibody specific for VEGF receptor 2 (VEGFR2), inhibits VEGF-A, -C and -D binding to VEGFR2 and inhibits ligand-induced mitogenesis of human endothelial cells. We evaluated candidate tumor (HER2, VEGFR2) and serum (VEGF-C, -D, and soluble [s] VEGFR1 and 3) biomarkers for correlation with overall survival (OS) and progression-free survival (PFS) in patients from the randomized phase 3 REGARD trial (NCT00917384) that demonstrated survival benefits for RAM vs. PL. Methods: Of 355 patients randomized to RAM or PL in REGARD, there was at least one evaluable biomarker result for 152 (43%) patients using VEGFR2 immunohistochemistry (IHC) or HER2 (IHC or fluorescence in situ hybridization [FISH]) in baseline tumor tissue samples. For 32 (9%) patients, baseline serum samples were analyzed using VEGF-C, -D, sVEGFR1 or 3 validated assays. Assay analyses were blinded. Results: The table provides the results of the HER2 analyses in tumor tissue (N = 147) and VEGFR2 analyses in tumor blood vessels (N = 143). The small number of patients with serum samples limited interpretation for candidate circulating biomarkers. Conclusions: Exploratory candidate biomarker analysis of tumor biopsies and serum from REGARD patients did not identify a significant predictive marker for RAM efficacy. Further examination of the role of VEGFR2 pathway biomarkers is warranted in ongoing RAM trials. Clinical trial information:NCT00917384
|
HER2+a |
HER2+a |
HER2- a |
HER2- a |
||
|
mOSb |
5.1 |
2.8 |
6.6 |
4.5
|
|
|
95% CI |
1.3-9.6 |
1.3-6.7 |
5.5-8.5 |
2.5-6.4
|
|
|
|
High |
High |
HR |
Low |
Low |
HR |
|
|
mOS b |
6.6 |
2.3 |
0.69 |
5.6 |
4.5 |
0.73
|
|
|
95% CI |
5.0-9.3 |
1.5-4.8 |
0.38-1.22 |
3.4-7.1 |
2.6-6.7 |
0.42-1.26
|
|
|
mPFS b |
2.8 |
1.3 |
0.35 |
2.2 |
1.9 |
0.73
|
|
|
95% CI |
1.5-4.1 |
1.1-1.3 |
0.20-0.59 |
1.4-2.8 |
1.3-2.7 |
0.42-1.27
|
|
Note: Treatment-by-VEGFR2 interaction p-values, not adjusted for multiplicity, were 0.878 for mOS and 0.051 for mPFS. Abbreviations: CI=confidence interval; HR=hazard ratio; m=median. aBang et al. 2010 criteria. bin months. cHigh= ≥ median H-score (35); low= <35.
Datum přednesení příspěvku: 1. 6. 2015
