癌症科学家发布具有里程碑意义的“菜篮子”研究计划成果

  近日，发表于国际杂志New England Journal of Medicine上的研究论文中，来自斯隆凯特林癌症纪念中心的科学家宣布了“菜篮子”研究计划的首轮研究结果，该研究计划主要基于患者机体肿瘤的特殊突变来探究患者对药物的反应。
  研究者Jose Baselga表示，我们对来自全球22个中心的122名患者进行了研究，观察了多重非黑色素瘤BRAFV600突变的癌症患者对药物维罗非尼（Vemurafenib）的反应，此前研究认为维罗非尼可以治疗BRAFV600突变的的黑色素瘤，然而截至今日尽管治疗效果非常显著，但研究者依然并不清楚维罗非尼治疗非黑色素瘤的效果。
  菜篮子计划允许同时对多种类型肿瘤活动的早期信号进行检测，同时也充分考虑到了肿瘤谱系对药物敏感性的影响，这项研究旨在基于癌症的突变来行来解析患者对疗法的反应，同时也可以帮助鉴别出不同癌症类型潜在的活性信号，相关研究结果或可以帮助寻找不同的药物靶点及开发新型的疗法治疗多种癌症。
  这项研究阐明了维罗非尼治疗多种非黑色素瘤BRAFV600突变的癌症的初步临床疗效，在122名临床参与者中研究者在多种肿瘤类型中都观察到了临床疗效；研究者在非小细胞肺癌及脂质肉芽肿病中观察到了维罗非尼的初步治疗效果，非小细胞肺癌的反应率及平均无进展生存期分别为42%和7.3个月。
  最后David Hyman博士说道，这项研究或可提供一种新型方法来研究罕见的肿瘤，如今我们对大部分癌症类型中所有的常见致癌突变进行了蓝图的绘制，而且我们也非常清楚在某些癌症中存在很多基因经常发生突变，但在另外一些癌症中却突变很少，下一步我们将会去寻找合适的药物组合来更深入地进行癌症等疾病发病机制的研究。 （转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations
NEJM    DOI: 10.1056/NEJMoa1502309
David M. Hyman, M.D., Igor Puzanov, M.D., Vivek Subbiah, M.D., Jason E. Faris, M.D., Ian Chau, M.D., Jean-Yves Blay, M.D., Ph.D., Jürgen Wolf, M.D., Ph.D., Noopur S. Raje, M.D., Eli L. Diamond, M.D., Antoine Hollebecque, M.D., Radj Gervais, M.D., Maria Elena Elez-Fernandez, M.D., Antoine Italiano, M.D., Ph.D., Ralf-Dieter Hofheinz, M.D., Manuel Hidalgo, M.D., Ph.D., Emily Chan, M.D., Ph.D., Martin Schuler, M.D., Susan Frances Lasserre, M.Sc., Martina Makrutzki, M.D., Florin Sirzen, M.D., Ph.D., Maria Luisa Veronese, M.D., Josep Tabernero, M.D., Ph.D., and José Baselga, M.D., Ph.D.
BACKGROUND
BRAF V600 mutations occur in various nonmelanoma cancers. We undertook a histology-independent phase 2 “basket” study of vemurafenib in BRAF V600 mutation–positive nonmelanoma cancers.
METHODS
We enrolled patients in six prespecified cancer cohorts; patients with all other tumor types were enrolled in a seventh cohort. A total of 122 patients with BRAF V600 mutation–positive cancer were treated, including 27 patients with colorectal cancer who received vemurafenib and cetuximab. The primary end point was the response rate; secondary end points included progression-free and overall survival.
RESULTS
In the cohort with non–small-cell lung cancer, the response rate was 42% (95% confidence interval [CI], 20 to 67) and median progression-free survival was 7.3 months (95% CI, 3.5 to 10.8). In the cohort with Erdheim–Chester disease or Langerhans’-cell histiocytosis, the response rate was 43% (95% CI, 18 to 71); the median treatment duration was 5.9 months (range, 0.6 to 18.6), and no patients had disease progression during therapy. There were anecdotal responses among patients with pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma, salivary-duct cancer, ovarian cancer, and clear-cell sarcoma and among patients with colorectal cancer who received vemurafenib and cetuximab. Safety was similar to that in prior studies of vemurafenib for melanoma.
CONCLUSIONS
BRAF V600 appears to be a targetable oncogene in some, but not all, nonmelanoma cancers. Preliminary vemurafenib activity was observed in non–small-cell lung cancer and in Erdheim–Chester disease and Langerhans’-cell histiocytosis. The histologic context is an important determinant of response in BRAF V600–mutated cancers. (Funded by F. Hoffmann–La Roche/Genentech; ClinicalTrials.gov number, NCT01524978.)