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
Topics Biomarkers
Breast Cancer, Metastatic
Presenter Luca Gianni
Authors L. Gianni1, A. Chan2, M. Mansutti3, X. Pivot4, R. Greil5, L. Provencher6, S. Prot7, N. Moore8, S.J. Scherer9, C. Pallaud10
  • 1Medical Oncology, IRCCS San Raffaele, 20132 - Milano/IT
  • 2Breast Clinical Trials Unit, Mount Hospital, 6000 - Perth/AU
  • 3Oncology, University Hospital S. Maria Misericordia, 33100 - Udine/IT
  • 4Service Oncologie Medicale, C.H.U. Jean Minjoz, FR-25030 - Besancon CEDEX/FR
  • 5Head Of The Iiird Medical Department, Paracelsus University Hospital Salzburg, AT-5020 - Salzburg/AT
  • 6Centre Des Maladies Du Sein Deschenes-fabia, CHA-Hôpital du Saint-Sacrement, Quebec/CA
  • 7Pdc, F Hoffmann-La Roche Ltd, 4070 - Basel/CH
  • 8Biostatistics, F Hoffmann-La Roche Ltd, 4070 - Basel/CH
  • 9Pharma Development, Genentech, Inc., 94080 - South San Francisco/US
  • 10Pharma Development Oncology Business, F Hoffmann-La Roche Ltd, 4070 - Basel/CH

Abstract

Background

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.

Table: 1657P

TH BV + TH HR (95% CI) Interaction p valuea
Subgroup Events/pts, n Median, mo Events/pts, n Median, mo
All 64/82 11.2 66/80 16.5 0.78 (0.56–1.11)
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-A L 33/45 13.6 30/36 16.5 0.83 (0.50–1.36) 0.795
H 31/37 8.5 35/43 16.6 0.70 (0.43–1.14)
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.