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作者:肿瘤瞭望 时间:2016/6/27 18:52:54    加入收藏
 关键字:ASCO 美国临床肿瘤学会 脑转移瘤多学科管理  

  在美国临床肿瘤学会(ASCO)年会的脑转移瘤的多学科管理专场,克利夫兰诊所(Cleveland Clinic)的肿瘤学家Manmeet Singh Ahluwalia,MD作报告“Targeted Therapy in Brain Metastases: Ready for Prime Time?(脑转移瘤的靶向治疗的黄金时代是否来临 )”。








  我的研究小组对比了ALK或EGFR突变脑转移瘤患者和野生型患者的治疗结果。我们发现。 EGFR 突变肺癌患者的总生存率已经提高,约为20个月,野生型是9-12个月。ALK阳性患者的OS提高更显著,总生存超过4年,过去ALK阳性患者的总生存预期是6-12月。






  基于最近研究结果,我们已经确定了脑转移患者的新治疗模式。我们主张个体化治疗,根据脑转移的多少、引发脑转移瘤的癌症类型(肺癌、乳腺癌、黑色素瘤)、基因检测结果,多学科治疗团队(放射肿瘤学家、医疗肿瘤学家和神经神经外科医生等)为患者制定合适的治疗方案,根据靶向突变的基因检测结果选择靶向治疗药物。免疫疗法越来越多地被用于脑转移瘤治疗,有研究显示,PD-1/CTLA-4抗体药物治疗脑转移瘤的缓解率 与其他部位肿瘤的治疗效果相似。



  Oncology Frontier: Could you please talk about the role of targeted therapy in Brain Metastase?




  Dr Ahluwalia: Brain metastases are a common clinical problem that we see every day when we treat patients with cancer. The incidence of brain metastases is increasing every day due to the increased use of imaging, increased participation in clinical trials, as well as patients doing better with their systemic cancers. As patients live longer, they develop brain metastases because the central nervous system is a sanctuary site. It is estimated that 200-300 thousand patients will develop brain metastases in the United States each year. The three most common cancers that go to the brain are lung cancer, breast cancer and melanoma. Lung cancer is the most common cause of brain metastases in the United States and around 50% of patients with brain metastases have a lung origin. A number of these patients have mutations that are now accessible with novel drugs that can get to the brain, and as a result, are changing the treatment paradigm of this patient population. For example, EGFR mutation is seen in 10% of the Caucasian population, but can occur in up to 35% of the East Asian population.


  There are a number of targeted therapies that are FDA approved for this patient profile. They include gefitinib, erlotinib, afatinib and more recently osimertinib. The new generation compounds like osimertinib have better blood-brain penetration compared to the earlier generation drugs like erlotinib or gefitinib. There has been some exciting data with these drugs that has been presented at ASCO this year showing intriguing results in patients with EGFR mutations. Similarly, 5% of patients with lung cancer harbor ALK mutations. There are a number of compounds that are FDA approved for this patient population including crizotinib and the new generation drugs, ceritinib and alectinib. The response rates seen with ceritinib and alectinib in initial studies are around 40-60%. These are very impressive results compared to prior chemotherapies, which did not have a good blood-brain penetration, of around 5-10% at best for most regimens.


  As our patients are living longer, it is more important to redefine how we treat these patients. Traditionally, patients with brain metastases were treated with radiation-based techniques or surgical resections. Radiation techniques included whole-brain irradiation, stereotactic radiosurgery or other focused forms of radiation. These days, there are a number of ongoing trials combining radiation or focused forms of radiation with some of the novel drugs I mentioned earlier. There are also drugs being designed that actually reach the brain. One example is ANG1005, which is being presented here at ASCO. This is a drug where three molecules of paclitaxel are covalently linked to Angiopep, which is a peptide that helps it get across the blood-brain barrier using the LRP-1 transport system. Initial results with this drug show a clinical benefit is seen in 70% of patients treated. Overall survival in this patient population is 35 weeks, which compares favorably with similar patients with this profile. Patients with HER2-positive disease are treated with this compound.


  There is another presentation that our group has been involved with concerning the outcomes in patients with brain metastases harboring ALK or EGFR mutations compared to those with wild type. What we found is that lung cancer patients who have EGFR mutations have an improved overall survival. In our group, the overall survival in this patient population was around twenty months compared to 9-12 months in those with wild type lung cancer mutations. These results are even more impressive in the ALK-positive patients where we are seeing survival exceeding four years. Traditionally, someone who has lung cancer brain metastases was expected to live six to twelve months.


  What is also very interesting is the use of immunotherapy in treating patients with brain metastases. A number of drugs are showing efficacy in brain metastases comparable to what has been seen elsewhere in the body. So we are redefining how we treat patients with brain metastases with the increased use of targeted therapies and immunotherapy compared to the prior use of chemotherapy. There will still be an ongoing role for focused forms of radiation and whole-brain radiation in the management of this patient population. I chaired a session yesterday in which it was outlined that the multidisciplinary management of patients with brain metastases gives the best outcomes for this patient population.






  我的研究小组对比了ALK或EGFR突变肺癌脑转移瘤患者和野生型患者的治疗结果。我们发现。 EGFR 突变肺癌患者的总生存率已经提高,约为20个月,野生型是9-12个月。ALK阳性患者的OS提高更显著,总生存超过4年,过去ALK阳性患者的总生存预期是6-12月。




  Oncology Frontier: According to ASCO 2016, Is there any progress that may change practice in the treatment of Brain Metastases from NSCLC?




  Dr Ahluwalia: Based on the results of some of the recent studies that have been presented elsewhere and at ASCO, we have been determining the new treatment paradigms for patients with brain metastases. We need to recognize that each patient is unique. We need to look at how functional the patient is, how many brain metastases they have, the type of cancer causing the brain metastases (lung cancer, breast cancer or melanoma), and accordingly, in consultation with radiation oncologists, medical oncologists and neurosurgeons, adopt an appropriate treatment plan for that patient. We are in the era of precision medicine where genomic profiling is routinely available for most patients at rates that are affordable. We need to see if someone has an actionable mutation and if so, use a targeted agent to help treat that patient. Immunotherapies are increasingly being used in the management of this patient population. Studies have shown that the response rates in brain metastases are very similar to what are seen in the rest of the body with the use of anti-PD-1 agents, as well as anti-CTLA-4 agents in melanoma.



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