Array CGH and DNA sequencing to personalise therapy for patients with metastatic breast cancer

Results of the prospective UNICANCER SAFIR-01 study performed in 400 patients with metastatic breast cancer, indicate that whole genome technologies can be equally delivered across hospitals, produce robust results and can identify a high rate of unexpected, targetable genomic alterations. In this study, a number of patients has already been selected for a specific targeted therapy based on the observed genomic alterations and promising, early signs of anti-tumor activity have been reported in this heavily pretreated group of patients.

Breast cancer cells harbour a large number of actionable genomic alterations, each characterising a rare genomic entity. In the UNICANCER SAFIR-01 study, array comparative genomic hybridization (aCGH) and Sanger sequencing were used to identify these genomic alterations and direct patients to specific targeted agents directed against the disturbed signaling pathways.

In the pre-SAFIR pilot study, the feasibility of performing whole genome profiling on a large number of samples in different hospitals was assessed. Once this pilot study demonstrated that this approach was feasible, 400 patients with metastatic breast cancer, without progressive disease on treatment, were included in the SAFIR-01 trial. Biopsies were taken from bone metastases and were analysed using whole genome aCGH and hot-spot mutation analysis for PI3KCA and AKT. Once patients demonstrate disease progression they are treated with a targeted agent directed against the signaling pathway that is disturbed by the genomic alteration. The study is being conducted in 18 French centres using 5 different aCGH platforms.

For 251 of the 423 patients that had signed in on the study at the time of the analysis an interpretable whole genome analysis was obtained. In 69% (N=172) of these patients a genomic alteration was observed for which a targeted therapy exists. The majority of these patients are still not in need of the investigational agent as they don’t have progressive disease. At the time of the presentation, 26 patients have been treated with a ‘matching targeted therapy’. The investigators expect that a total of 80 patients will be treated with a matched targeted agent within three years. Interestingly, 8 of the 26 patients that have already received a targeted agent show evidence of response or disease stabilization. Given the highly pre-treated nature of the patient population in this study, this is a very promising result.

In summary, this is the first, large prospective study evaluating the use of whole genome technologies for cancer care. It demonstrates that whole genome analyses can be equally delivered across hospitals, produce robust results and can identify targetable genomic alterations. Interestingly, the evaluated approach resulted in early signs of anti-tumor activity. As such, this study suggests that it is time to bring personalised medicine to the field of cancer care. Countering this optimism, the investigators do indicate that there is still room for improvement. First of all, molecular testing is difficult on bone biopsies and the biopsies often contain a low percentage of tumor cells. More importantly, the access to targeted agents outside the setting of a clinical trial should be improved in order to make this treatment approach feasible.

Reference

André F, Bachelot T, Campone M et al. Array CGH and DNA sequencing to personalize therapy for metastatic breast cancer: A prospective National trial (UNICANCER SAFIR-01). Presented at ESMO 2012, Abstract LBA13.