The Breadth of Precision Medicine at ASCO 2019: From early detection to progress in difficult-to-treat cancers and previously undruggable targets

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General Views Attendees and speakers
[Source: ASCO/Max Gersh 2019

The way ASCO started for me this year set the scene for what was an inspiring and fascinating weekend. Early on Friday morning, before most people’s ASCOs had started, I sat in a meeting room in the conference center watching it slowly fill to the brim with people. I was there to participate in a panel discussion on precision oncology, organized by McKinsey & Co. My fellow panel members represented a broad range of perspectives and backgrounds, and it was a lively and engaging discussion that I hope to be able to continue in some form through this forum another time.

Despite our differing perspectives and roles, it struck me that we were all strongly aligned around one point in particular—the belief that our ability to properly harness the power of real-world data will have the greatest influence on progress in cancer care in the future.

We also agreed that simply generating huge quantities of data is not the answer. I think we can all appreciate, after an ASCO full of too many coffees and sandwiches on the run, that performance is very much dependent on the quality of the fuel, and the same is true here. To shape our collective understanding and decision making, the data at our disposal has to be of exceptionally high quality—and consistently so.

That this was a unifying priority was heartening for me and there was a real spirit of collaboration in the room centered around achieving that goal.

As a result, I went into ASCO eagerly anticipating the possibilities on offer at this year’s meeting, and it certainly didn’t disappoint. The sheer volume of new knowledge and thinking presented over the course of a few days was astounding, but there were some announcements in particular that stood out for me this year.

Glimpsing a future of early detection

I was not alone in being impressed and encouraged by the data that Grail presented from its Circulating Cell-free Genome Atlas study, demonstrating the potential for its developmental multi-cancer early detection blood test. The test was able to show robust detection in a group of 12 cancers at early stages of disease, as well as identify the tissue of origin in 90% of cases.

General Views Attendees and speakers
[Source: ASCO/Max Gersh 2019]
Every single one of us that work in this field wants to see the day arrive when the early detection of all cancers is not just possible, it’s routine. I believe these data brought us one step closer to that day, and the buzz felt throughout the congress echoed that belief.

For us, the details of the announcement had additional meaning too, as they provided further validation of techniques and approaches that have potential across many other branches of precision medicine. It was encouraging to see the accuracy and specificity that can be achieved through testing markers of epigenetic gene regulation, such as DNA methylation, as these data provide important insights that validate approaches we and others are taking in the research setting.

Biomarkers front and center once again

Another highlight of my ASCO was seeing so many examples that reinforced just how essential biomarkers have become and how, as a field, we have embraced a biomarker-led approach so quickly and with such positive outcomes. It seems incredible that even five years ago the predominant focus for therapy development was still around broad approaches for large populations. To be where we are today—with biomarkers leading the charge when it comes to progress—is a huge achievement.

Pinpointing the right patients for PDL-1 inhibition

One stand-out example for me was the updated analysis of the IMpassion130 trial in advanced triple negative breast cancer (TNBC). The original study results showed no statistically significant survival benefit for atezolizumab plus nab-paclitaxel compared to placebo at 18 months; results that would have signaled the end of the line a few years ago. But this new analysis in PDL-1 positive patients found a substantial clinically meaningful overall survival benefit of seven months. Furthermore, more than half of the atezolizumab patients were alive at two years compared to 37% of patients taking placebo.

These results are significant because they clearly strengthen the argument for baseline testing at the point of diagnosis. In fact, for me it can no longer be a question of if we test; it has to be about how, when and, if we’re not already testing, why not? It’s a win-win. If we test, we are able to guide physicians in immediate clinical decision making with concrete evidence, potentially improving patient outcomes. If we collect and pool those outcomes from as large a patient population as possible, we can apply the data to help guide physicians’ clinical decision making at a population level, accelerate discovery, and optimize existing approaches. We can also identify the cross-walk between driver mutations and pathways to open up therapeutic avenues across tumor types, or suggest new combination strategies. In essence, providing the fuel that will keep the engine of discovery driving us forward and, in doing so, fundamentally changing the future for people who are yet to be diagnosed with cancer.

Some much needed progress in pancreatic cancer

Results from the POLO study also reinforced the benefits of a biomarker-led approach, this time in pancreatic cancer. Pancreatic cancer is characterized by poor outcomes, partly due to a lack of targets for precision therapeutics and a reliance on chemotherapy. Germline mutations in the BRCA1/2 genes play a pivotal role in the development and progression of pancreatic cancer and POLO is the first randomized phase III study to apply this knowledge to a biomarker-led therapeutic approach. The study demonstrated that maintenance therapy with the PARP inhibitor olaparib nearly halved the risk of disease progression after chemotherapy versus placebo in BRCA-mutated pancreatic cancers. This is not only encouraging news for pancreatic cancer patients, but it provides yet more evidence for the utility, and thus the need for, routine testing at the point of diagnosis and should help to redefine the standard of care for this type of cancer.

Drugging the undruggable

From difficult-to-treat cancers to ‘undruggable’ targets, one announcement from Amgen held significance for me and many others that went beyond the results of the study. The ubiquity of KRAS mutations in so many cancers has made it one of the most researched—and frustratingly elusive—targets in precision medicine. But early data for Amgen’s KRAS inhibitor show us that good things might come to those who wait. In a small Phase I study of 10 heavily pretreated colorectal and lung cancer patients, results demonstrated that the drug halted tumor growth in the majority of patients, and shrank tumors in half of those with lung cancer.

It was a very small study, and there is a long way to go before a KRAS inhibitor reaches the clinic, so why all the excitement? This is not just a potential watershed moment for KRAS inhibition—to me it embodies the tipping point for precision medicine I’ve touched upon before and highlights the decades of research and thinking that have brought us to where we are today.
All of these examples serve to demonstrate how far we have come in such a short time. The sheer number of biomarker-led approaches that are being explored or validated today would have seemed unimaginable a few years ago, and the benefits of that research are being felt by scientists, physicians, regulators, and of course, patients.

Harmonizing the future of data

But this is a tipping point, not a finale. How do we ensure that we move toward a future where we can maintain and build on the progress we are making? One final announcement from ASCO concerns perhaps one of the most important challenges we face and brings us back to the panel discussion that kicked off my ASCO this year. If the quality and depth of data is key to the future of precision medicine, how do we find a way to harmonize the reporting, collection, integration, and security of that data across sites and across borders?

With this in mind, I was encouraged to see the launch of mCODE, or ‘Minimal Common Oncology Data Elements’, a joint collaboration between ASCO and a number of stakeholders. The premise of the project is that the variability of electronic health record software makes it difficult to capture and pool data into a central resource. mCODE is an initial set of data standards covering domains such as disease, genomics, treatment, and outcomes and is free to download at mCODEinitiative.org. The aim is to create a common language between sites—and eventually across borders—that will harmonize the way we collect data. I see this as a step in the right direction, and an example of how collaboration across the oncology landscape can deliver solutions to some of the challenges we face.

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