Lancet Oncology:个性化抗癌药疗效与传统治疗无差异,但专家仍看好
随着基因组测序成本的下降,肿瘤学家开始研发以病人基因为靶标的昂贵新药。然而近日发表在《 Lancet Oncology》的研究表明,个性化抗癌药物的疗效与比传统治疗相比,并无多大差异。

随着基因组测序成本的下降,肿瘤学家开始研发以病人基因为靶标的昂贵新药。然而近日发表在《 Lancet Oncology》的研究表明,个性化抗癌药物的疗效与比传统治疗相比,并无多大差异。

芝加哥大学肿瘤学家Daniel Catenacci认为对个性化抗癌药物疗效的验证很重要,因为目前越来越多的肿瘤学家专注这领域。本研究第一作者,巴黎居里研究所肿瘤学家Christophe Le Tourneau表示,在现实生活中,未经过临床验证的试验很常见。同时他对此现象表示理解,因为病人想要存活而医生也想提供帮助。然而,给肿瘤基因突变患者以未获批的个性化药物治疗可使研究进入更好的临床阶段。




休斯顿德克萨斯大学MD安德癌症研究中心的肿瘤学家Apostolia Tsimberidou表示,该研究证明了个性化医疗试验随机性的可行性。但在她看来,这次试验的设计比较糟糕,因为晚期疾病患者可能从个性化医疗中受益。同时她还表示,该试验没有选择最好的药物作为评估对象,并依赖于一个简单的方法来与癌症突变匹配。

本研究作者Le Tourneau承认这点,但他指出目前市场上还未出现更好的药物,且许多肿瘤学家运用同样简单的方法来在做个性化治疗决策。Catenacci也认为目前许多癌症医生在药物和病人匹配决策上做得不够。如果能准确将适合的药物匹配给合适的病人,那么精准医疗会变得更好。



今年6月,美国国家癌症研究所宣布招募1000名志愿者来参与精准医疗项目,该项目名为 NCI-MATCH,在该项目中志愿者将根据肿瘤基因突变情况来接受20种药物治疗。美国临床肿瘤学会还推出了一个名为TAPUR的注册表,用于收集病人接受针对性抗癌药物的数据情况。

Catenacci说,如果有任何研究显示个性化抗癌药物对患者有效,无论这些药物是否获特定组织批准都会带来严重的监管挑战。Le Tourneau补充道,个性化医疗面临这些挑战只是时间上的问题。医生最终会根据患者肿瘤的遗传分子来量身定制治疗方案,而不是针对身体中的肿瘤组织。


Use of personalized cancer drugs runs ahead of the science

  • Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial

    Background Molecularly targeted agents have been reported to have anti-tumour activity for patients whose tumours harbour the matching molecular alteration. These results have led to increased off-label use of molecularly targeted agents on the basis of identified molecular alterations. We assessed the efficacy of several molecularly targeted agents marketed in France, which were chosen on the basis of tumour molecular profiling but used outside their indications, in patients with advanced cancer for whom standard-of-care therapy had failed. Methods The open-label, randomised, controlled phase 2 SHIVA trial was done at eight French academic centres. We included adult patients with any kind of metastatic solid tumour refractory to standard of care, provided they had an Eastern Cooperative Oncology Group performance status of 0 or 1, disease that was accessible for a biopsy or resection of a metastatic site, and at least one measurable lesion. The molecular profile of each patient's tumour was established with a mandatory biopsy of a metastatic tumour and large-scale genomic testing. We only included patients for whom a molecular alteration was identified within one of three molecular pathways (hormone receptor, PI3K/AKT/mTOR, RAF/MEK), which could be matched to one of ten regimens including 11 available molecularly targeted agents (erlotinib, lapatinib plus trastuzumab, sorafenib, imatinib, dasatinib, vemurafenib, everolimus, abiraterone, letrozole, tamoxifen). We randomly assigned these patients (1:1) to receive a matched molecularly targeted agent (experimental group) or treatment at physician's choice (control group) by central block randomisation (blocks of size six). Randomisation was done centrally with a web-based response system and was stratified according to the Royal Marsden Hospital prognostic score (0 or 1 vs 2 or 3) and the altered molecular pathway. Clinicians and patients were not masked to treatment allocation. Treatments in both groups were given in accordance with the approved product information and standard practice protocols at each institution and were continued until evidence of disease progression. The primary endpoint was progression-free survival in the intention-to-treat population, which was not assessed by independent central review. We assessed safety in any patients who received at least one dose of their assigned treatment. This trial is registered with, number NCT01771458. Findings Between Oct 4, 2012, and July 11, 2014, we screened 741 patients with any tumour type. 293 (40%) patients had at least one molecular alteration matching one of the 10 available regimens. At the time of data cutoff, Jan 20, 2015, 195 (26%) patients had been randomly assigned, with 99 in the experimental group and 96 in the control group. All patients in the experimental group started treatment, as did 92 in the control group. Two patients in the control group received a molecularly targeted agent: both were included in their assigned group for efficacy analyses, the patient who received an agent that was allowed in the experimental group was included in the experimental group for the purposes of safety analyses, while the other patient, who received a molecularly targeted agent and chemotherapy, was kept in the control group for safety analyses. Median follow-up was 11·3 months (IQR 5·8–11·6) in the experimental group and 11·3 months (8·1–11·6) in the control group at the time of the primary analysis of progression-free survival. Median progression-free survival was 2·3 months (95% CI 1·7–3·8) in the experimental group versus 2·0 months (1·8–2·1) in the control group (hazard ratio 0·88, 95% CI 0·65–1·19, p=0·41). In the safety population, 43 (43%) of 100 patients treated with a molecularly targeted agent and 32 (35%) of 91 patients treated with cytotoxic chemotherapy had grade 3–4 adverse events (p=0·30). Interpretation The use of molecularly targeted agents outside their indications does not improve progression-free survival compared with treatment at physician's choice in heavily pretreated patients with cancer. Off-label use of molecularly targeted agents should be discouraged, but enrolment in clinical trials should be encouraged to assess predictive biomarkers of efficacy.

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