1657P - Biomarker (BM) results from the phase III AVEREL trial of 1st-line bevacizumab (BV), trastuzumab (H) + docetaxel (T) for HER2-positive locally recur...
|Date||30 September 2012|
|Event||ESMO Congress 2012|
|Session||Poster presentation II|
Breast Cancer, Metastatic
L. Gianni1, A. Chan2, M. Mansutti3, X. Pivot4, R. Greil5, L. Provencher6, S. Prot7, N. Moore8, S.J. Scherer9, C. Pallaud10
AVEREL efficacy and safety results have been reported. We present exploratory analyses from the optional BM substudy.Methods
Patients (pts) with HER2-positive LR/mBC received 1st-line T (100 mg/m2 q3w) + H (8 → 6 mg/kg q3w) ± BV (15 mg/kg q3w). The primary endpoint was investigator-assessed PFS. Baseline (BL) blood and tissue samples were collected from consenting pts. BL plasma levels of candidate BMs were measured using a novel ELISA. Median BL values for each BM were used to define high (> median; H) vs low (≤ median; L) BM cohorts and to correlate BMs with PFS using Cox regression corrected for prognostic factors.Results
Plasma samples were available from 162/424 pts (38%). ICAM-1 correlated statistically significantly with PFS at α = 0.05.
|TH||BV + TH||HR (95% CI)||Interaction p valuea|
|Subgroup||Events/pts, n||Median, mo||Events/pts, n||Median, mo|
|E-selectin||L H||31/44 32/37||16.4 8.2||30/36 35/43||16.5 16.6||1.01 (0.61–1.68) 0.57 (0.35–0.92)||0.241|
|IL-8||L H||35/45 28/36||13.6 8.4||28/35 37/44||16.4 17.8||0.84 (0.51–1.40) 0.74 (0.45–1.22)||0.506|
|ICAM-1||L H||30/45 33/36||16.4 10.3||29/35 36/44||16.5 16.2||1.13 (0.68–1.89) 0.49 (0.30–0.80)||0.017|
|bFGF||L H||32/41 31/40||13.3 11.1||33/39 32/40||16.4 19.1||0.80 (0.49–1.30) 0.80 (0.49–1.32)||0.837|
|PDGF-C||L H||29/40 35/42||17.1 8.5||32/41 34/39||16.5 16.6||0.87 (0.52–1.44) 0.72 (0.45–1.16)||0.342|
|VEGF-C||L H||35/42 29/40||13.5 9.6||32/39 34/41||14.8 19.1||0.70 (0.43–1.15) 0.92 (0.56–1.51)||0.649|
|VEGFR-1||L H||30/40 33/41||11.1 13.3||33/40 32/39||16.2 16.6||0.76 (0.46–1.25) 0.84 (0.52–1.37)||0.982|
|VEGFR-2||L H||35/44 28/37||11.2 11.0||30/36 35/43||13.7 19.2||0.95 (0.58–1.55) 0.67 (0.40–1.10)||0.174|
|VEGFR-3||L H||35/48 28/33||12.2 11.0||25/32 40/47||15.3 16.6||0.88 (0.52–1.47) 0.65 (0.40–1.06)||0.051|
aModel includes prognostic factors.Conclusions
High BL ICAM-1 correlated significantly with greater PFS benefit from BV at α = 0.05, consistent with data in lung cancer. VEGF-A, VEGFR-2 and -3 and E-selectin showed potential predictive value. VEGF-A and VEGFR-2 results are in line with data in HER2-negative mBC and pancreatic cancer.Disclosure
L. Gianni: LG acts as a Consultant and has sat on Advisory Boards for Roche, Genentech, GSK, Novartis, Pfizer, Boehringer Ingelheim, Astra Zeneca, and Celgene.
A. Chan: AC has acted as a Consultant, sat on Advisory Boards, and received honoraria and research funding from Roche.
X. Pivot: XP has acted as a Consultant and sat on Advisory Boards for Roche, Eisai and GlaxoSmithKline, and has received honoraria from Sanofi.
R. Greil: RG has acted as a Consultant for, sat on Advisory Boards for, and received honoraria and research funding from Roche.
L. Provencher: LP has received a travel grant and honoraria from Roche.
S. Prot: SP is an employee of F Hoffmann-La Roche Ltd.
N. Moore: NM is an employee and holds stock in F Hoffmann-La Roche Ltd.
S.J. Scherer: SS is an employee of Genentech.
C. Pallaud: CP is an employee of F Hoffmann-La Roche Ltd. .
All other authors have declared no conflicts of interest.