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专家说临床试验对于转移性CRC的进展至关重要

2017-12-14493
Shubham Pant，MD根据Shubham Pant博士的说法，转移性结直肠癌（CRC）患者的三线治疗选择基本归结为regorafenib（Stivarga）和TAS-102（Lonsurf）.CRC是一种恶性肿瘤，含有许多基因突变/例如RAS，BRAF，微卫星不稳定性（MSI）和HER2 / neu。这些突变可以作为开发靶向药物的途径，随着下一代测序的快速进展，这个领域的治疗药物的发展现在比以往任何时候都更有可能，他补充说。在2017年的OncLive＆reg ;德州大学安德森癌症中心的副教授Pant博士介绍了“胃肠癌的科学峰会”，讨论了转移性结直肠癌患者的治疗选择。“我们应该考虑在这些患者失败后的早期阶段进行分析，在线治疗，只是为了看看有没有可用的治疗方法“裤子解释。 “医生应该被纳入CRC的所有临床试验中，因为有不少目标正在进行中。我们需要个性化治疗，因为我们确实需要弄清楚可行的突变，谁可以得到帮助，哪些患者可以产生影响。“在这次活动的采访中，Pant强调了临床的重要性试验作为在这种环境下建立更多新颖治疗决定的途径.OncLive：请提供关于转移性结直肠癌的讲座的概述。喘息：我们在前两行中有[治疗选项]，但是在第三行中，我们没有有这么多的选择。但是，更多的选择正在制定中。我们基本上有两种选择，regorafenib和TAS-102，但是我的整个谈话集中在我们将要从这里开始 - 在三线环境中，CRC的新兴治疗，靶向治疗和免疫治疗。您如何接近第三对于转移患者的在线治疗RC？通常情况下，在这之前，我们试图对患者进行一些分析，比如下一代测序。我们尝试确定目标，但显然这取决于绩效状态如何 - 它必须非常好。然后，我们尝试为他们确定一个可用于靶向治疗的临床试验。目前在临床试验中正在探索哪些方案看起来很有前途？“馅饼”的三线CRC是一个很大的馅饼，但是如果将其分解成BRAF突变型疾病，HER2 / neu阳性和MSI高级CRC等专业，我们可以在所有类别中找到新的治疗方法。免疫疗法在其他一些靶向疗法中起作用，并且一些[肿瘤需要]联合疗法。在该领域是令人兴奋的时期，因为即使在三线环境中，转移性CRC也是非常强健的在那里他们有良好的表现 - 他们的肝脏和肺脏工作很好 - 所以我们需要为他们找到更多的治疗方法。我的一个同事Scott Kopetz博士在2017年ASCO年会上介绍了vemurafenib （Zelboraf），用于黑色素瘤，加上西妥昔单抗（Erbitux）和伊立替康在BRAF突变CRC中。对于那些以前一切难以忍受的患者，反应率都很高。这些患者最迫切的需求是什么？我们需要开发新的治疗方法，并确定可行的靶点，我们可以进入这个靶点，他们可以得到长期或稳定的疾病控制。以前，我们以前总是看反应速度，虽然这仍然很重要，但是我们试图瞄准的其中一个目标是控制疾病，使我们看到更长的无恶化生存期。这是病人可以活着几个月，几年没有进展，我相信，这是最终的目标。你如何看待在未来5到10年的治疗进展？[我明白]这些工作的组合，例如至于BRAF突变体CRC，w与vemurafenib联合西妥昔单抗和伊立替康组合。然而，单药的好例子，如MSI高度CRC，其中单药pembrolizumab（Keytruda）和nivolumab（Opdivo）都显示出前景。下一代测序对这一患者群体有什么影响这有很大的影响。我们可以确定一些目标;我们可以在干草堆里寻找那根针。显然，一些数据还在逐渐成熟，我们只会到数据所在的位置。它已经产生了很大的影响，但我们需要更多的数据才能确定影响到底有多大。


Shubham Pant, MD Third-line treatment options for patients with metastatic colorectal cancer (CRC) essentially boil down to regorafenib (Stivarga) and TAS-102 (Lonsurf), according to Shubham Pant, MD.CRC is a malignancy that harbors many genetic mutations/aberrations, such as RAS, BRAF, microsatellite instability (MSI), and HER2/neu. These mutations serve as a road in which to develop targeted agents and, with the rapid progress of next-generation sequencing, the development of therapeutics in this arena is more of a possibility now than it has ever been, he adds.During the 2017 OncLive® State of the Science SummitTM on Gastrointestinal Cancers, Pant, an associate professor of The University of Texas MD Anderson Cancer Center, discussed therapeutic options for patients with metastatic CRC.“We should consider profiling for these patients early when they are failing their second-line therapy, just to see if there are available therapies out there,” Pant explained. “Physicians should be clued into all of the clinical trials that are going on in CRC, because there are quite a few going on hitting different targets. We need to individualize treatment, because we truly need to figure out the actionable mutation[s], who can be helped, and in which patients we can make an impact.”In an interview during the event, Pant stressed the importance of clinical trials as an avenue to establish more novel treatment decisions in this setting. OncLive: Please provide an overview of your lecture on metastatic CRC. Pant: We have [treatment options] in the first 2 lines but, in the third line, we do not have so many options. However, more options are being developed. We have 2 options essentially, regorafenib and TAS-102, but my whole talk focused on wher we are going to go from here—the emerging therapies, targeted therapies, and immunotherapies for CRC in the third-line setting. How do you approach third-line treatment for a patient with metastatic CRC? Normally, before that, we try to get some profiling on the patient such as next-generation sequencing. We try to identify targets but, obviously, this depends on how the performance status is—it has to be really good. Then, we try to identify a clinical trial for them that we can use for targeted therapy.  What regimens currently being explored in clinical trials look promising? The “pie” of third-line CRC is a big pie, but if you break it down into specialties, such as BRAF-mutant disease, HER2/neu-positive, and MSI-high CRC, we can find new therapies in all categories. Immunotherapy works in some, targeted therapies work in others, and some [tumors require] a combination.It is an exciting time in the field, because these patients with metastatic CRC, even in the third-line setting, are very robust in a way wher they have excellent performance status—their liver and lungs work great—so we need to try to find more therapies for them. One of my colleagues, Dr Scott Kopetz, presented data at the 2017 ASCO Annual Meeting of the combination of vemurafenib (Zelboraf), which is used in melanoma, plus cetuximab (Erbitux) and irinotecan in BRAF-mutant CRC. There were great response rates in patients who had been refractory to everything else prior. What is the most pressing unmet need for these patients? We need to develop new therapies and identify actionable targets, wher we can go in and hit the mutation well so that they can get prolonged or stable disease control. Previously, we used to always look at response rate and, while that is still important, one of the things that we are trying to target is controlling the disease so that we see a longer progression-free survival. This is so the patient can live months and years without progressing and that, I believe, is the ultimate goal.  How do you see treatments progressing in the next 5 to 10 years? [I see] combinations [that] work, such as for BRAF-mutant CRC, with the combination of vemurafenib plus cetuximab and irinotecan. However, there are good examples of single agents, such as in MSI-high CRC in which the single agents pembrolizumab (Keytruda) and nivolumab (Opdivo) are both showing promise.  What impact has next-generation sequencing had on this patient population? It has had a great impact. We can identify some targets; we can look for that needle in a haystack. Obviously, some of the data are still maturing, and we'll just go to wher the data take us. It has made a big impact, but we need a lot more data to come in before we can say for sure how big the impact has been.


http://www.onclive.com/web-exclusives/expert-says-clinical-trials-are-essential-for-progress-in-metastatic-crc

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