|资讯|癌症精准治疗：DNA匹配可以显着提高生存率
最新重大突破研究结果显示，通过对肿瘤DNA进行个体化分析，化疗患者可能会延长生存率六倍。医生确定选择癌症精准治疗方法越来越依靠肿瘤的基因检测结果和导向了。
这在新一代基因测序技术普及应用的今天，无疑是为所有患者带来一次难得的机会。
在未来几年内，科学家和医生们将通过更多真实环境下的临床治疗结果数据来评估DNA基因指导下的化疗方法。
该研究是由著名的MD安德森癌症中心Tsimberidou教授主导的，她评述说“我们需要知道是什么原因导致癌症，更需要了解如何针对每一种正确的治疗方法。Tsimberidou教授在最近的美国临床癌症协会年会发表她的团队和协作完成的最新研究成果。详细内容如下：
MD Anderson’s precision medicine study findsapproach successful across tumor types
Matchingtargeted therapies to tumor-specific gene mutations across tumor types improvedprogression-free survival (PFS) and overall survival (OS) in patients withadvanced disease relative to those receiving non-matched treatment (NMT),according to research from The MD Anderson Cancer Center. The researchers also found that receivingmatched targeted therapy (MTT) was an independent factor for predicting longerOS.
Long-termdata from IMPACT show that the three-year OS was 15% in the MTT groupcompared to 7% in the NMT group. The 10-year OS was 6 percent in the MTTgroup, compared to 1% in the NMT group. Apostolia M.Tsimberidou, professor of Investigational CancerTherapeutics, presented the findings on the press program at the2018 American Society for Clinical Oncology Annual Meeting.
The study isthe first and largest precision medicine trial to look at survival and has thelongest follow-up of any such trial.
MD Andersonopened IMPACT in 2007 after her experience with the targeted therapy Gleevecshowed how it changed both the treatment and survival rates for chronic myeloidleukemia (CML), once a deadly disease.
“When weopened IMPACT, it was viewed as incredibly novel. Because of the variability,frequency and rarity of alterations in specific solid tumor types, it wasthought it would be difficult to use molecular testing for clinical trialselection, without taking into consideration any specific characteristics”.
“However, gleaning from our Gleevec-CML experience, we hypothesized thatgenetic and molecular analysis of solid tumors also could enable the selectionof optimal therapy for patients with solid tumors.”
The umbrellaprotocol enrolled 3,743 MD Anderson patients from 2007 to 2013. All werereferred to MD Anderson’s Phase I program with end-stage disease. The patients’median age was 57 years, with a range in age from 16 to 86. The ratio of womento men was 61 to 39%, respectively. The most common cancers treated weregastrointestinal, gynecologic, breast, melanoma and lung, with the rest beingmore rare types.
As expectedin this population, patients were heavily pre-treated; the median number ofprior therapies received was four, with some being treated with any many as 16previous therapies.
All 3,743patients enrolled in IMPACT received molecular testing; 1,307 were found tohave at least one molecular alteration, with 711 receiving MTT (with or withoutchemotherapy) and 596 receiving NMT. The majority of IMPACT participants whoreceived MTT received an investigational drug then being tested in a clinicaltrial; others received an FDA-approved targeted therapy commercially approvedfor another indication.
In those who received MTT, the median PFS was 4 months and the medianOS was 9.3 months, compared to 2.8 months and 7.3 months, respectively, inthose who received NMT.
Given thequantity of patients enrolled and the length of follow-up, the MD Andersonresearchers were able to analyze the different pathways that predicted responsein the MTT groups.
Given thenumber of patients in the trial and the length of follow-up, the investigatorswere able to develop a prognostic score to predict OS. Taking intoconsideration all baseline characteristics in the 1,307 patients who receivedmolecular testing, the absence of liver metastases, normal LDH levels, normalfunctional status, albumin levels and platelet counts were all found to beindependent factors for longer OS.
Most interestingly, said Tsimberidou,receiving MTT was also found to be an independent factor associated with longerOS.
In contrast,shorter survival was associated with liver metastases, elevated LDH levels,poor functional status, low albumin levels, elevated platelet counts, and age60 years or older. In addition, molecular alterations in the PI3K/AKT/mTORpathway were an independent factor predicting shorter overall survival comparedto other alterations.
When type oftherapy was added to the model, NMT was found to be an independent factorpredicting shorter survival.
IMPACT’sfollow-up study, IMPACT2, is a randomized Phase II looking at PFS and isongoing. Tsimberidou noted that the advances from IMPACT to IMPACT2, likenext-generation sequencing technologies, and the use of immune features and newdrugs, including immunotherapy, are staggering.
“When IMPACT firstopened, we tested for no more than one-to-two genes” . “Now patientsare being tested for hundreds of actionable genes, amplifications andmutations, as well as for immune markers.
Ideally, in the future, patients’tumor testing and cell-free DNA analysis will become the standard of care atthe time of diagnosis, in hopes of making a difference for patients upfront,especially in those with hard-to-treat cancers.”
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