Philippe L. Bedard

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Recent therapeutic advances in oncology have been driven by the identification of tumour genotype variations between patients, called interpatient heterogeneity, that predict the response of patients to targeted treatments. Subpopulations of cancer cells with unique genomes in the same patient may exist across different geographical regions of a tumour or(More)
Compared with treatment options for early-stage breast cancer, few data exist regarding the optimal use of chemotherapy for metastatic breast cancer (MBC). The choice of using a combination of cytotoxic chemotherapies vs sequential single agents is controversial. At the 6th European Breast Cancer Conference, the European School of Oncology Metastatic Breast(More)
Gene expression profiling has led to a new molecular classification of breast cancer characterized by four intrinsic subtypes: basal-like, HER2-positive, luminal A, and luminal B. Despite expressing estrogen receptor, the luminal-B subtype confers increased risk of early relapse with endocrine therapy compared with the luminal-A subtype. Although luminal-B(More)
PURPOSE To establish the recommended phase II dose of the oral γ-secretase inhibitor RO4929097 (RO) in combination with gemcitabine; secondary objectives include the evaluation of safety, tolerability, pharmacokinetics, biomarkers of Notch signaling and preliminary anti-tumor activity. METHODS Patients with advanced solid tumors were enrolled in cohorts(More)
BACKGROUND The Notch signalling pathway has been implicated in tumour initiation, progression, angiogenesis and development of resistance to vascular endothelial growth factor (VEGF) targeting, providing a rationale for the combination of RO4929097, a γ-secretase inhibitor, and cediranib, a VEGF receptor tyrosine kinase inhibitor. METHODS Patients(More)
BACKGROUND To determine the recommended phase II dose (RP2D) and assess the safety, pharmacokinetics (PKs) and pharmacodynamics of RO4929097in combination with temsirolimus. METHODS Escalating doses of RO4929097 and temsirolimus were administered at three dose levels. Patients received once daily oral RO4929097 on a 3 days on/4 days off schedule every(More)
BACKGROUND overexpression of HER-2 is observed in 15-25% of breast cancers, and is associated with increased risk of recurrence. Current guidelines recommend trastuzumab and chemotherapy for most HER-2-positive patients. However, the majority of patients does not recur and might thus be overtreated with adjuvant systemic therapy. We investigated whether the(More)
BACKGROUND Patient selection for phase I trials (PIT) in oncology is challenging. A typical inclusion criterion for PIT is 'life expectancy > 3 months', however the 90 day mortality (90DM) and overall survival (OS) of patients with advanced solid malignancies are difficult to predict. METHODS We analyzed 233 patients who were enrolled in PIT at Princess(More)
Through the use of surrogate markers of efficacy, neoadjuvant studies may facilitate the implementation of new treatments into clinical practice. However, disease-free survival is the current standard outcome endpoint for registration of a novel treatment. The coupling of smaller neoadjuvant 'proof of principle' studies with larger adjuvant registration(More)
Large-scale collaborative initiatives using next-generation DNA sequencing and other high-throughput technologies have begun to characterize the genomic landscape of breast cancer. These landmark studies have identified infrequent driver mutations that are potential targets for therapeutic intervention with approved or investigational drug treatments, among(More)