Array CGH and DNA sequencing to personalize targeted treatment of metastatic breast cancer (MBC) patients (pts): A prospective multicentric trial (SAFIR01).

Abstract

511 Background: The aim of the present study was to profile the metastatic lesion of pts using high throughput technologies, and to treat them accordingly. Methods: SAFIR01 trial aimed to include 400 pts with MBC, selected for not presenting a progressive disease at the time of biopsy. A biopsy was done in a metastatic site. DNA was extracted if the tumor contained >50% cancer cells, and sent to one of the 5 genomic centers who performed array CGH (copy number changes) and sanger sequencing on PIK3CA (exon 10/21) and AKT1 (exon 3). A targeted therapy matched to the genomic alteration was expected to be proposed at the time of progressive disease. The primary endpoint was the % of pts who received a targeted therapy according to the genomic alteration. Results: A biopsy of metastatic site was done successfully in 408 out of the 423 included pts. Biopsy was complicated by a serious adverse event in 9 pts. A discrepancy between primary and metastatic lesion was observed in 8% and 19% of pts for Her2 and HR. Array CGH and sequencing were successfully obtained in 277 (68%) and 295 (72%) pts. The main reason for failure of genomic test was the low cellularity (n=93). A targetable genomic alteration was identified in 204 pts. The most frequent genomic alterations were PIK3CA mutations, CCND1, FGF4 and FGFR1 amplifications. 76 pts presented a rare targetable genomic alteration (<5%), including AKT1 mutations, EGFR, FGFR2, PIK3CA, MDM2 amplifications. Early Feb 2013, 4 6 out of 277 pts with genomic analyses (17%) had received a targeted therapy matched to the genomic alteration, covering twelve different targets. Updated results on number of pts treated, together with efficacy data will be presented. Next generation sequencing on metastatic lesions is ongoing and results will be presented. Conclusions: This trial evaluated the concept of personalized medicine for MBC and provided a large scale genomic analysis of metastatic tissue. This study suggests that assessing the biology of metastatic tissue could allow driving pts to targeted therapy. A randomized trial (SAFIR02) testing this approach is expected to start during summer 2013. Clinical trial information: NCT01414933.