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Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER).
Lancet Oncol 2014; 15(3):267-74LO

Abstract

BACKGROUND

Breast cancer is characterised by genomic alterations. We did a multicentre molecular screening study to identify abnormalities in individual patients with the aim of providing targeted therapy matched to individuals' genomic alterations.

METHODS

From June 16, 2011, to July 30, 2012, we recruited patients who had breast cancer with a metastasis accessible for biopsy in 18 centres in France. Comparative genomic hybridisation (CGH) array and Sanger sequencing on PIK3CA (exon 10 and 21) and AKT1 (exon 4) were used to assess metastatic biopsy samples in five centres. Therapeutic targets were decided on the basis of identified genomic alterations. The primary objective was to include 30% of patients in clinical trials testing a targeted therapy and, therefore, the primary outcome was the proportion of patients to whom a targeted therapy could be offered. For the primary endpoint, the analyses were done on the overall population registered for the trial. This trial is registered with ClinicalTrials.gov, number NCT01414933.

FINDINGS

423 patients were included, and biopsy samples were obtained from 407 (metastatic breast cancer was not found in four). CGH array and Sanger sequencing were feasible in 283 (67%) and 297 (70%) patients, respectively. A targetable genomic alteration was identified in 195 (46%) patients, most frequently in PIK3CA (74 [25%] of 297 identified genomic alterations), CCND1 (53 [19%]), and FGFR1 (36 [13%]). 117 (39%) of 297 patients with genomic tests available presented with rare genomic alterations (defined as occurring in less than 5% of the general population), including AKT1 mutations, and EGFR, MDM2, FGFR2, AKT2, IGF1R, and MET high-level amplifications. Therapy could be personalised in 55 (13%) of 423 patients. Of the 43 patients who were assessable and received targeted therapy, four (9%) had an objective response, and nine others (21%) had stable disease for more than 16 weeks. Serious (grade 3 or higher) adverse events related to biopsy were reported in four (1%) of enrolled patients, including pneumothorax (grade 3, one patient), pain (grade 3, one patient), haematoma (grade 3, one patient), and haemorrhagic shock (grade 3, one patient).

INTERPRETATION

Personalisation of medicine for metastatic breast cancer is feasible, including for rare genomic alterations.

FUNDING

French National Cancer Institute, Breast Cancer Research Foundation, Odyssea, Operation Parrains Chercheurs.

Authors+Show Affiliations

Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France; INSERM Unit U981, Institut Gustave Roussy, Villejuif, France; Université Paris Sud, le Kremlin Bicêtre, France. Electronic address: fabrice.andre@gustaveroussy.fr.Departement de Cancerologie Medicale, Université Lyon 1, Centre Léon Bérard, Lyon, France.INSERM Unit U981, Institut Gustave Roussy, Villejuif, France.Institut de Cancérologie de l'Ouest/René Gauducheau, Nantes Saint Herblain, France.Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France; INSERM Unit U981, Institut Gustave Roussy, Villejuif, France.Department of Medical Oncology, Institut Curie, Paris, France.Institut Claudius Regaud, Department of Pathology, Toulouse, France.Department of Translational Research, Institut Gustave Roussy, Villejuif, France.Centre Léon Bérard, Lyon, France; Université Lyon 1, Lyon, France; ProfileXpert, SFR Lyon-Est, Lyon, France.Department of Translational Research, Institut Curie, Paris, France.Molecular Oncology Department, Institut Paoli Calmettes, Marseille, France.Department of Medical Oncology, Institut Claudius Regaud, Toulouse, France.Department of Medical Oncology, Institut Paoli Calmettes, Marseille, France.Department of Medical Oncology, Centre François Baclesse, Caen, France.Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France.Department of Medical Oncology, Centre Oscar Lambret, Lille, France.Department of Medical Oncology, Centre Eugène Marquis, Rennes, France.Research and Development Unit, UNICANCER, Paris, France.Department of Biostatistics, Institut Claudius Regaud, Toulouse, France.Department of Medical Oncology, Institut Bergonié, Université de Bordeaux, INSERM U916, Bordeaux, France.

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24508104

Citation

André, Fabrice, et al. "Comparative Genomic Hybridisation Array and DNA Sequencing to Direct Treatment of Metastatic Breast Cancer: a Multicentre, Prospective Trial (SAFIR01/UNICANCER)." The Lancet. Oncology, vol. 15, no. 3, 2014, pp. 267-74.
André F, Bachelot T, Commo F, et al. Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER). Lancet Oncol. 2014;15(3):267-74.
André, F., Bachelot, T., Commo, F., Campone, M., Arnedos, M., Dieras, V., ... Bonnefoi, H. (2014). Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER). The Lancet. Oncology, 15(3), pp. 267-74. doi:10.1016/S1470-2045(13)70611-9.
André F, et al. Comparative Genomic Hybridisation Array and DNA Sequencing to Direct Treatment of Metastatic Breast Cancer: a Multicentre, Prospective Trial (SAFIR01/UNICANCER). Lancet Oncol. 2014;15(3):267-74. PubMed PMID: 24508104.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER). AU - André,Fabrice, AU - Bachelot,Thomas, AU - Commo,Frederic, AU - Campone,Mario, AU - Arnedos,Monica, AU - Dieras,Véronique, AU - Lacroix-Triki,Magali, AU - Lacroix,Ludovic, AU - Cohen,Pascale, AU - Gentien,David, AU - Adélaide,Jose, AU - Dalenc,Florence, AU - Goncalves,Anthony, AU - Levy,Christelle, AU - Ferrero,Jean-Marc, AU - Bonneterre,Jacques, AU - Lefeuvre,Claudia, AU - Jimenez,Marta, AU - Filleron,Thomas, AU - Bonnefoi,Hervé, Y1 - 2014/02/07/ PY - 2014/2/11/entrez PY - 2014/2/11/pubmed PY - 2014/5/21/medline SP - 267 EP - 74 JF - The Lancet. Oncology JO - Lancet Oncol. VL - 15 IS - 3 N2 - BACKGROUND: Breast cancer is characterised by genomic alterations. We did a multicentre molecular screening study to identify abnormalities in individual patients with the aim of providing targeted therapy matched to individuals' genomic alterations. METHODS: From June 16, 2011, to July 30, 2012, we recruited patients who had breast cancer with a metastasis accessible for biopsy in 18 centres in France. Comparative genomic hybridisation (CGH) array and Sanger sequencing on PIK3CA (exon 10 and 21) and AKT1 (exon 4) were used to assess metastatic biopsy samples in five centres. Therapeutic targets were decided on the basis of identified genomic alterations. The primary objective was to include 30% of patients in clinical trials testing a targeted therapy and, therefore, the primary outcome was the proportion of patients to whom a targeted therapy could be offered. For the primary endpoint, the analyses were done on the overall population registered for the trial. This trial is registered with ClinicalTrials.gov, number NCT01414933. FINDINGS: 423 patients were included, and biopsy samples were obtained from 407 (metastatic breast cancer was not found in four). CGH array and Sanger sequencing were feasible in 283 (67%) and 297 (70%) patients, respectively. A targetable genomic alteration was identified in 195 (46%) patients, most frequently in PIK3CA (74 [25%] of 297 identified genomic alterations), CCND1 (53 [19%]), and FGFR1 (36 [13%]). 117 (39%) of 297 patients with genomic tests available presented with rare genomic alterations (defined as occurring in less than 5% of the general population), including AKT1 mutations, and EGFR, MDM2, FGFR2, AKT2, IGF1R, and MET high-level amplifications. Therapy could be personalised in 55 (13%) of 423 patients. Of the 43 patients who were assessable and received targeted therapy, four (9%) had an objective response, and nine others (21%) had stable disease for more than 16 weeks. Serious (grade 3 or higher) adverse events related to biopsy were reported in four (1%) of enrolled patients, including pneumothorax (grade 3, one patient), pain (grade 3, one patient), haematoma (grade 3, one patient), and haemorrhagic shock (grade 3, one patient). INTERPRETATION: Personalisation of medicine for metastatic breast cancer is feasible, including for rare genomic alterations. FUNDING: French National Cancer Institute, Breast Cancer Research Foundation, Odyssea, Operation Parrains Chercheurs. SN - 1474-5488 UR - https://www.unboundmedicine.com/medline/citation/24508104/Comparative_genomic_hybridisation_array_and_DNA_sequencing_to_direct_treatment_of_metastatic_breast_cancer:_a_multicentre_prospective_trial__SAFIR01/UNICANCER__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1470-2045(13)70611-9 DB - PRIME DP - Unbound Medicine ER -