Routine molecular profiling of cancer: results of a one-year nationwide program of the French Cooperative Thoracic Intergroup (IFCT) for advanced non-small cell lung cancer (NSCLC) patients.

Fabrice Barlesi 1, * Julien Mazières 2 Jean-Philippe Merlio 3 Didier Debieuvre 4 Jean Mosser 5 Hervé Léna 6, 7 L'Houcine Ouafik 8 Benjamin Besse 9 Isabelle Rouquette 10 Virginie Westeel 11 Fabienne Escande 12 Isabelle Monnet 13 Antoinette Lemoine 14 Rémi Veillon 15 Hélène Blons 16 Clarisse Audigier-Valette 17 Pierre-Paul Bringuier 18 Régine Lamy 19 Michèle Beau-Faller 20 Jean-Louis Pujol 21, 22 Jean-Christophe Sabourin 23 Frédérique Penault-Llorca 24 Marc G Denis 25 Sylvie Lantuejoul 26, 27 Franck Morin 28 Quân Tran 28 Pascale Missy 28 Alexandra Langlais 28 Bernard Milleron 29 Jacques Cadranel 30 Jean-Charles Soria 9 Gérard Zalcman 31
* Corresponding author
18 Equipe 4
CRCL - Centre de Recherche en Cancérologie de Lyon
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, 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.
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Routine molecular profiling of...
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Fabrice Barlesi, Julien Mazières, Jean-Philippe Merlio, Didier Debieuvre, Jean Mosser, et al.. Routine molecular profiling of cancer: results of a one-year nationwide program of the French Cooperative Thoracic Intergroup (IFCT) for advanced non-small cell lung cancer (NSCLC) patients.. Lancet, Elsevier, 2016, 287 (10026), pp.1415-1426. ⟨10.1016/S0140-6736(16)00004-0⟩. ⟨hal-01259217⟩



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