Ruppert Anne-Marie, Beau-Faller Michèle, Debieuvre Didier, Ouafik L'Houcine, Westeel Virginie, Rouquette Isabelle, Mazières Julien, Bringuier Pierre-Paul, Monnet Isabelle, Escande Fabienne, Ricordel Charles, Merlio Jean-Philippe, Janicot Henri, Lemoine Antoinette, Foucher Pascal, Poudenx Michel, Morin Franck, Langlais Alexandra, Souquet Pierre-Jean, Barlesi Fabrice, Wislez Marie
GRC n°04, Theranoscan, AP-HP, Groupe Hospitalier Sorbonne Université, Hôpital Tenon, Paris, France.
Department of Pneumology, AP-HP, Groupe Hospitalier Sorbonne Université, Hôpital Tenon, Paris, France.
JTO Clin Res Rep. 2020 May 15;1(3):100052. doi: 10.1016/j.jtocrr.2020.100052. eCollection 2020 Sep.
mutations are detected in 20% to 30% of NSCLC. However, mutation subtypes may differently influence the outcome of patients with advanced NSCLC.
In the Biomarkers France study, 4894 mutations (26.2%) were detected in 4634 patients from the 17,664 enrolled patients with NSCLC. Survival and treatment data on noncurative stage III to IV NSCLC were available for 901 patients. First- and second-line treatment effects on progression-free survival and overall survival were analyzed according to the mutations subtype.
Over 95% of patients with mutation were smokers or former smokers who were white (99.5%), presenting with adenocarcinoma (82.5%). The most common mutation subtype was G12C (374 patients; 41.5%), followed by G12V (168; 18.6%), G12D (131; 14.5%), G12A (62; 6.9%), G13C (45; 5.0%), G13D (31; 3.4%), and others (10; 1%). Approximately 21% of patients had transition mutation and 68.2% had a transversion mutation. G12D and transition mutations were predominant in never-smokers. The median overall survival for patients with -mutated NSCLC was 8.1 months (95% confidence interval [CI]: 7.5-9.5), without any differences according to the different subtypes mutations. The median progression-free survival was 4.6 months (95% CI: 4.2-5.1) for first-line treatment and 4.8 months (95% CI: 4.3-6.8) for second-line treatment, without any differences according to the different subtypes mutations.
mutation subtypes influenced neither treatment responses nor outcomes. The G12C mutation was detected in 41.5% of patients, who are now eligible for potent and specific G12C inhibitors.
在20%至30%的非小细胞肺癌(NSCLC)中可检测到突变。然而,突变亚型可能对晚期NSCLC患者的预后产生不同影响。
在法国生物标志物研究中,从17664名入组的NSCLC患者中,在4634名患者中检测到4894个突变(26.2%)。901名非治愈性III至IV期NSCLC患者可获得生存和治疗数据。根据突变亚型分析一线和二线治疗对无进展生存期和总生存期的影响。
超过95%的有突变的患者为吸烟者或既往吸烟者,为白人(99.5%),患有腺癌(82.5%)。最常见的突变亚型是G12C(374例患者;41.5%),其次是G12V(168例;18.6%)、G12D(131例;14.5%)、G12A(62例;6.9%)、G13C(45例;5.0%)、G13D(31例;3.4%)和其他(10例;1%)。约21%的患者有转换突变,68.2%有颠换突变。G12D和转换突变在从不吸烟者中占主导。有突变的NSCLC患者的中位总生存期为8.1个月(95%置信区间[CI]:7.5 - 9.5),根据不同的突变亚型没有差异。一线治疗的中位无进展生存期为4.6个月(95% CI:4.2 - 5.1),二线治疗为4.8个月(95% CI:4.3 - 6.8),根据不同的突变亚型没有差异。
突变亚型既不影响治疗反应也不影响预后。41.5%的患者检测到G12C突变,这些患者现在有资格使用强效且特异性的G12C抑制剂。