Assistance Publique Hôpitaux de Marseille, Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Centre d'Investigation Clinique, Marseille, France.
Hôpital Larrey, Centre Hospitalier Universitaire, Université Paul Sabatier, Toulouse, France.
Lancet. 2016 Apr 2;387(10026):1415-1426. doi: 10.1016/S0140-6736(16)00004-0. Epub 2016 Jan 15.
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.
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.
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.
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.
French National Cancer Institute (INCa).
在常规治疗中，建议对晚期非小细胞肺癌（NSCLC）患者进行已知致癌驱动因素的分子谱分析。然而，在全国范围内，该政策的可行性及其对结果的影响尚不清楚。我们旨在评估在法国国家癌症研究所资助的全国性计划下，在一年内通过 28 个认证的区域遗传中心进行常规筛查的患者的特征、分子谱和临床结果。
本研究包括晚期 NSCLC 患者，他们通过法国 28 个认证的区域遗传中心常规筛查 EGFR 突变、ALK 重排以及 HER2（ERBB2）、KRAS、BRAF 和 PIK3CA 突变。在 2012 年 4 月至 2013 年 4 月的一年内连续评估患者。我们测量了六个常规筛查基因中分子改变的频率、获得分子结果的周转时间以及患者的临床结果。本研究在 ClinicalTrials.gov 上注册，编号为 NCT01700582。
对 17664 名 NSCLC 患者的 18679 次分子分析进行了研究（已知数据患者的中位年龄为 64.5 岁[范围 18-98]，65%为男性，81%为吸烟者或前吸烟者，76%为腺癌）。分析开始到书面报告提供的中位间隔为 11 天（IQR 7-16）。大约 50%的分析记录了遗传改变；在 17706 份可提供数据的分析中，报告了 1947 例（11%）EGFR 突变、98 例（1%）HER2 突变、4894 例（29%）KRAS 突变、262 例（2%）BRAF 突变、252 例（2%）PIK3CA 突变和 388 例（5%）ALK 重排。在分析时，中位随访时间为 24.9 个月（95%CI 24.8-25.0）。遗传改变的存在影响了 8147 名患者中 4176 名（51%）的一线治疗，并且与一线治疗中实现总体反应的患者比例显著提高相关（存在遗传改变的患者为 37%[95%CI 34.7-38.2]，而不存在遗传改变的患者为 33%[29.5-35.6]；p=0.03），以及二线治疗（17%[15.0-18.8] vs 9%[6.7-11.9]；p<0.0001）。存在遗传改变还与改善一线无进展生存期（10.0 个月[95%CI 9.2-10.7] vs 7.1 个月[6.1-7.9]；p<0.0001）和总生存期（16.5 个月[15.0-18.3] vs 11.8 个月[10.1-13.5]；p<0.0001）相关，而不存在遗传改变。
对晚期非小细胞肺癌患者进行全国范围内的常规分子谱分析是可行的。遗传改变的频率、获得分析结果的可接受周转时间以及检测遗传改变提供的临床优势表明，该政策具有临床益处。
法国国家癌症研究所（INCa）。
