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Ann Oncol. 2019 Mar 13. pii: mdz080. doi: 10.1093/annonc/mdz080. [Epub ahead of print]

Molecular screening program to select molecular-based recommended therapies for metastatic cancer patients: analysis from the ProfiLER trial.

Author information

1
Department of Medical Oncology & University Claude Bernard, Léon Bérard Cancer Center, Lyon, France.
2
Department of Translational Research and Innovation, Léon Bérard Cancer Center, Lyon, France.
3
Department of Medical Oncology, Léon Bérard Cancer Center, Lyon, France.
4
Department of BioPathology, Léon Bérard Cancer center, Lyon, France.
5
Department of Medical Oncology, Lyon Sud Hospital Center, CITOHL, Institute of Cancerology, Hospices Civils de Lyon (IC-HCL), Lyon, France.
6
EMR UCBL/HCL 3738, Faculty of Medicine-Lyon Sud, University of Lyon 1, Oullins, France.
7
Department of Medical Oncology, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France.
8
Department of Medical Oncology, Mutualist Hospital Group, Grenoble, France.
9
Synergie Lyon Cancer, Bio-Informatics Platform, Léon Bérard Cancer Center, Lyon, France.
10
Department of Clinical Research and Innovation, Léon Bérard Cancer Center, Lyon, France.

Abstract

BACKGROUND:

Antitumor activity of molecularly targeted agents (MTA) is guided by the presence of documented genomic alteration in specific histological subtypes. We aim to explore the feasibility, efficacy and therapeutic impact of molecular profiling in routine setting.

PATIENTS AND METHODS:

This multicentric prospective study enrolled adult or pediatric patients with solid or hematological advanced cancer previously treated in advanced/metastatic setting and non-eligible to curative treatment. Each molecular profile was established on tumor, relapse or biopsies, and reviewed by a molecular tumor board (MTB) to identify molecular-based recommended therapies (MBRT). The main outcome was to assess the incidence rate of genomic mutations in routine setting, across specific histological types. Secondary objectives included a description of patients with actionable alterations and for whom MBRT was initiated, and overall response rate.

RESULTS:

Four centers included 2579 patients from February 2013 to February 2017, and the MTB reviewed the molecular profiles achieved for 1980 (76.8%) patients. The most frequently altered genes were CDKN2A (N=181, 7%), KRAS (N=177, 7%), PIK3CA (N=185, 7%), and CCND1 (N=104, 4%). An MBRT was recommended for 699/2579 patients (27%), and only 163/2579 patients (6%) received at least one MBRT. Out of 182 lines of MBRT initiated, 23 (13%) partial responses were observed. However, only 0.9% of the whole cohort experienced an objective response.

CONCLUSION:

A MBRT was provided for 27% of patients in our study, but only 6% of patients actually received matched therapy with an overall response rate of 0.9%. Molecular screening should not be used at present to guide decision making in routine clinical practice outside of clinical trials.

KEYWORDS:

Advanced cancer; Molecular profiling; Molecular targeted agents; Precision medicine; decision-making

PMID:
30865223
DOI:
10.1093/annonc/mdz080

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