BO21129, A PHASE II STUDY OF ERLOTINIB IN. SECOND-LINE PANCREATIC CANCER: POTENTIAL ROLE. OF AMPHIREGULIN? Michel Ducreux1, Irina ...
oral presentations
Annals of Oncology
O-0006 Table 1
O
0007
EXPLORATORY SERUM BIOMARKER ANALYSES FROM BO21129, A PHASE II STUDY OF ERLOTINIB IN SECOND-LINE PANCREATIC CANCER: POTENTIAL ROLE OF AMPHIREGULIN?
Michel Ducreux1, Irina Davidenko2, David Propper3, Giovanni Gerardo Cardellino4, Avgust Garin5, John Bridgewater6, Minesh Jain7, Limas Kupcinskas8, Sufiya Safina9, Alberto Fittipaldo10, Walter Bordogna10, Carina Hillenbach11 and Barbara Klughammer11 1 Institut Gustave Roussy, Villejuif, 2Krasnodar City Oncology Center, Krasnodar, 3 Barts and the London, London, 4University Hospital of Udine, Udine, 5Russian Cancer Research Center, Moscow, 6University College London Hospital, London, 7Ruby Hall Clinic, Pune, Maharashtra, 8Lithuanian University of Health Sciences, Kaunas, 9Republic Clinical Oncology Dispensary, Kazan, Republic of Tartarstan, 10Roche Products Ltd, Welwyn Garden City, Hertfordshire, 11 F. Hoffmann-La Roche Ltd, Basel Introduction: Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor, is approved in combination with gemcitabine for advanced pancreatic cancer. As the use of biomarkers to guide treatment decisions for targeted therapies is an area of increasing interest, a post-approval commitment was made to investigate potential biomarkers for erlotinib in pancreatic cancer. This randomised, placebo-controlled, multicentre, phase II study examined whether any biomarkers were predictive of differential outcomes with erlotinib monotherapy in advanced pancreatic cancer. The primary data for this study have been presented previously and showed no correlation between any of the pre-specified biomarkers investigated and the primary endpoint of progression-free survival (PFS) with erlotinib. Here we present the results of exploratory analyses on serum biomarkers. Methods: Serum samples were collected from patients at baseline, 3 weeks, and after treatment discontinuation. Randomisation was stratified by ECOG PS, region and smoking status, and the initial estimation of hazard ratio for the treatment effect was
Volume 23 | Supplement 4 | June 2012
by unadjusted Cox regression. After observing imbalances in some baseline characteristics, additional post-hoc analyses using a stepwise model selection algorithm were performed to assess for any impact on PFS and OS. Serum biomarker analyses were conducted on amphiregulin, EGF, TGF-α, and sHer-2. Exploratory analyses of efficacy were performed in ‘low’ and ‘high’ subgroups, as compared to the median of each soluble marker in the overall population. Efficacy was analysed in subgroups using both the initial unadjusted analysis, as well as the post-hoc model that was developed in the overall population. Results: Data on baseline serum markers were available for 199 out of 207 patients for amphiregulin and TGF-α, and 202 out of 207 patients for EGF and sHer-2. The adjusted post-hoc analysis of serum biomarkers showed that erlotinib provided a significant benefit in terms of PFS and OS in patients with high levels of amphiregulin (Table). Validation of results for other markers is ongoing and data will be presented. Conclusion: Exploratory adjusted analyses of serum markers showed that patients with high serum amphiregulin concentrations achieved a significant benefit in both PFS and OS. The observation that patients with elevated baseline levels of amphiregulin obtained benefits in both PFS and OS with erlotinib may suggest potential for this biomarker in pancreatic cancer.
O-0007 Table 1
doi:10.1093/annonc/mds151 | iv
