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Lancet. 2016 Apr 2;387(10026):1415-1426. doi: 10.1016/S0140-6736(16)00004-0. Epub 2016 Jan 15.

Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT).

Author information

1
Assistance Publique Hôpitaux de Marseille, Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Centre d'Investigation Clinique, Marseille, France. Electronic address: fabrice.barlesi@ap-hm.fr.
2
Hôpital Larrey, Centre Hospitalier Universitaire, Université Paul Sabatier, Toulouse, France.
3
Centre Hospitalier Universitaire de Bordeaux, Pôle Biologie et Anatomie Pathologique, Pessac, France; Université de Bordeaux, Histologie et Pathologie Moléculaires des Tumeurs, Bordeaux, France.
4
Hôpital Emile Muller, Service de Pneumologie, Mulhouse, France.
5
Centre Hospitalier Universitaire de Rennes, Département de Génomique et Génétique Moléculaire, Plateforme INCA, Rennes, France.
6
Hôpital Pontchaillou, Service de Pneumologie, Centre Hospitalier Universitaire, Rennes, France.
7
Assistance Publique Hôpitaux de Marseille, Service de Transfert d'Oncologie Biologique, Aix Marseille University, Marseille, France.
8
Gustave Roussy, Cancer Campus, Villejuif, France; University Paris-Sud, Châtenay-Malabry, France.
9
Institut Universitaire du Cancer de Toulouse, Oncopôle, Service d'Anatomie Pathologique, Toulouse, France.
10
Université de Franche-Comté, EA3181, Centre Hospitalier Universitaire Jean Minjoz, Service de Pneumologie, Besançon, France.
11
Centre Hospitalier Universitaire de Lille, Département de Biochimie et Biologie Moléculaire, Centre de Biologie Pathologie, Lille, France.
12
Centre Hospitalier Intercommunal de Créteil, Service de Pneumologie et de Pathologie Professionnelle, Créteil, France.
13
Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier des Hôpitaux Universitaires Paris-Sud, Service d'Oncogénétique- Oncomolpath, Université Paris 11, Villejuif, France.
14
Centre Hospitalier Universitaire de Bordeaux, Service des Maladies Respiratoires, Pessac, France.
15
UMR-S1147, INSERM, Université Paris Descartes, Assistance Publique Hôpitaux de Paris Département de Biologie, Hôpital Européen Georges Pompidou, Paris, France.
16
Centre Hospitalier Sainte Musse, Service de Pneumologie, Toulon, France.
17
Hôpital Edouard Herriot, Service d'Anatomie et de Cytologie Pathologique, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon Cancer Research Center, UMR 1057 INSERM, Lyon, France.
18
Centre Hospitalier de Bretagne Sud, Service d'Oncologie Médicale, Lorient, France.
19
Centre Hospitalier Universitaire de Hautepierre, Laboratoire de Biochimie et de Biologie Moléculaire & Plate-forme de Génomique des Cancers, Strasbourg, France.
20
Centre Hospitalier Universitaire de Montpellier, Unité d'Oncologie Thoracique, Pôle Cœur Poumon, Hôpital Arnaud de Villeneuve, Montpellier, France.
21
Centre Hospitalier Universitaire de Rouen, Département d'Anatomie et de Cytologie Pathologiques, Rouen, France.
22
Centre Jean Perrin, Département d'Anatomie et de Cytologie Pathologique, Clermont-Ferrand, France.
23
Centre Hospitalier Universitaire de Nantes, Laboratoire de Biochimie, Nantes, France.
24
Centre Hospitalier Universitaire A Michallon, Département d'Anatomie et Cytologie Pathologiques DACP, Institut de Biologie et de Pathologie, Université Joseph Fourier-INSERM U 823, Institut Albert Bonniot, Grenoble, France.
25
Clinical Research Unit, French Cooperative Thoracic Intergroup (IFCT), Paris, France.
26
Biostatistics Unit, French Cooperative Thoracic Intergroup (IFCT), Paris, France.
27
Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Service de Pneumologie, Sorbonne Universités, UPMC Université Paris 06, Paris, France.
28
Centre Hospitalier Universitaire de Caen, Service de Pneumologie et Oncologie Thoracique, Centre de Recherche Clinique, Université de Caen-Basse Normandie, Caen, France.

Abstract

BACKGROUND:

The molecular profiling of patients with advanced non-small-cell lung cancer (NSCLC) for known oncogenic drivers is recommended during routine care. Nationally, however, the feasibility and effects on outcomes of this policy are unknown. We aimed to assess the characteristics, molecular profiles, and clinical outcomes of patients who were screened during a 1-year period by a nationwide programme funded by the French National Cancer Institute.

METHODS:

This study included patients with advanced NSCLC, who were routinely screened for EGFR mutations, ALK rearrangements, as well as HER2 (ERBB2), KRAS, BRAF, and PIK3CA mutations by 28 certified regional genetics centres in France. Patients were assessed consecutively during a 1-year period from April, 2012, to April, 2013. We measured the frequency of molecular alterations in the six routinely screened genes, the turnaround time in obtaining molecular results, and patients' clinical outcomes. This study is registered with ClinicalTrials.gov, number NCT01700582.

FINDINGS:

18,679 molecular analyses of 17,664 patients with NSCLC were done (of patients with known data, median age was 64·5 years [range 18-98], 65% were men, 81% were smokers or former smokers, and 76% had adenocarcinoma). The median interval between the initiation of analysis and provision of the written report was 11 days (IQR 7-16). A genetic alteration was recorded in about 50% of the analyses; EGFR mutations were reported in 1947 (11%) of 17,706 analyses for which data were available, HER2 mutations in 98 (1%) of 11,723, KRAS mutations in 4894 (29%) of 17,001, BRAF mutations in 262 (2%) of 13,906, and PIK3CA mutations in 252 (2%) of 10,678; ALK rearrangements were reported in 388 (5%) of 8134 analyses. The median duration of follow-up at the time of analysis was 24·9 months (95% CI 24·8-25·0). The presence of a genetic alteration affected first-line treatment for 4176 (51%) of 8147 patients and was associated with a significant improvement in the proportion of patients achieving an overall response in first-line treatment (37% [95% CI 34·7-38·2] for presence of a genetic alteration vs 33% [29·5-35·6] for absence of a genetic alteration; p=0·03) and in second-line treatment (17% [15·0-18·8] vs 9% [6·7-11·9]; p<0·0001). Presence of a genetic alteration was also associated with improved first-line progression-free survival (10·0 months [95% CI 9·2-10·7] vs 7·1 months [6·1-7·9]; p<0·0001) and overall survival (16·5 months [15·0-18·3] vs 11·8 months [10·1-13·5]; p<0·0001) compared with absence of a genetic alteration.

INTERPRETATION:

Routine nationwide molecular profiling of patients with advanced NSCLC is feasible. The frequency of genetic alterations, acceptable turnaround times in obtaining analysis results, and the clinical advantage provided by detection of a genetic alteration suggest that this policy provides a clinical benefit.

FUNDING:

French National Cancer Institute (INCa).

PMID:
26777916
DOI:
10.1016/S0140-6736(16)00004-0
[Indexed for MEDLINE]
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