From standard to personalised care

By Pierre Valette, Emmy and Peabody-Award winning journalist and TV producer

Before Dr. Chura had taken responsibility for her care, Christine’s prior oncologist had told her that she needed to “get her affairs in order.” Her ovarian cancer, which had been treated with debilitating standard-of-care chemotherapy, radiation, and multiple surgeries, had metastasized to her lymph nodes and her liver. Three months into Christine’s new treatment, Chura remembers “smiling from ear to ear, waiting to show her that her scans were now completely clear.”

“We changed the natural history of her disease,” says Chura. “Normally remissions get shorter and shorter, and they progress more aggressively with time. With Christine, she’s been in total remission since we started her treatment four years ago.”

The targeted treatment Christine received was identified in a report from Foundation Medicine Inc. (FMI), a molecular insights company based in Cambridge, Massachusetts. To generate the report, FMI conducted a thorough genomic profile of Christine’s cancer that revealed that the signaling pathways involving PIK3CA and PTEN were likely driving her cancer. The recommended treatment—approved originally for advanced kidney cancer—altered the course of Christine’s disease, and is still keeping her cancer in check.

“The amazing thing about the targeted therapy,” says Christine, “is that it doesn’t have the toxic side effects of my chemotherapy or radiation. I wasn’t supposed to be here, and now I’m able to watch my two daughters grow up.”

The walls of FMI’s lounge are filled with photographs of patients like Christine. She and the millions of others like her with advanced cancer are the reason the company was founded in 2010, with the goal of bringing cutting-edge science and technology to everyday cancer care.

At the time, genomic profiling for certain cancers was beginning to reveal effective, low-toxicity targeted therapies. But too few oncologists were giving patients genetic tests that might reveal more effective therapies based on the unique footprint of their disease. And the genomic profiling tests that were given usually focused on specific mutations, thereby running the risk of missing the actual targets that were causing the disease.

“Cancer is an incredibly complex disease,” says Vincent Miller, M.D., an oncologist who worked at Sloan-Kettering Medical Center for nearly two decades and is currently FMI’s chief medical officer. “So to presuppose that the smartest doctor can look at a specific patient and know the genes of interest is oversimplifying the analytical process required for each patient. By doing genomic tests one at a time, many oncologists were thinking in isolation, not connecting the dots, not thinking broadly.”

Long before the term “precision medicine” came into vogue, FMI developed an individualised approach that starts with high-fidelity agnostic genomic profiling for each patient. Unlike standard single marker tests—which assume the site of a cancer’s origin, and look for a specific genetic alteration—FMI’s test doesn’t presuppose knowledge of the cancer’s exact profile.

Instead, FMI’s begins by isolating the “alterations of interest” in the “genes of interest” using sophisticated algorithms that, in the words of FMI’s medical director Jeffrey Ross, M.D., “separate the wheat from the chaff.”

Once testing identifies a target genomic alteration, FMI’s clinical research team culls the world’s most up-to-date cancer research to recommend FDA- or EU-approved therapies or clinical trials for the specific alteration. It’s like “giving the doctor and the patient a precise roadmap to their therapy,” says FMI’s CEO, Troy Cox.

FMI’s approach was novel—and unproven—when it was first introduced. At the time, Cox says, the big question from many oncologists was: “is your test actionable?”

Seven years later, the company’s numbers speak for themselves. Of the 79,000 samples from cancer patients, FMI tested in 2017, 38% percent were matched with an FDA approved therapy, 83% percent were matched with at least one relevant clinical trial, and all of them had at least one of those two outcomes.

By contrast, more than 60 percent of advanced cancer patients today fail to undergo genomic testing—and are often relegated to highly toxic and ineffective therapies.

FMI’s genomic tests have also proven to be more comprehensive than many of the ones that are currently used, which in some cases has led to more accurate results. For instance, in a recent study1, researchers conducted an FMI analysis of lung cancer patients for whom third party single-marker tests had previously yielded an ALK negative result. The analysis revealed that 35 percent of those patients were actually ALK positive, and 70 percent of those responded positively to an ALK-targeted therapy.

Bryce Olson, a patient advocate whose life was prolonged by genomic profiling and subsequent targeted treatment, says that patient-specific genomic tests “give cancer patients keys to a whole new kingdom. As an advanced cancer patient, you need options, you need hope. It empowers you and engages you in your own care a lot more than the standard of care, which might not work.”

FMI’s approach not only benefits patients, but the more than 40 bio-pharma clients with whom they partner throughout each stage of drug research and development, from target discovery to commercial launch.

Far from running a victory lap, though, FMI realizes that they have a long way to go to fulfilling the vision of of getting the right drug to the right patient at the right time. The first challenge is to increase access to comprehensive genomic profiling for cancer patients. “It’s inexcusable that more advanced cancer patients don’t have access,” says Troy Cox. As a result, many patients are living shorter, less productive lives.” Dr. Miller refers to this challenge as “democratizing” access, with the promise of comprehensive genomic profiling moving beyond “ivory tower institutions” and made available to all.

The second challenge is to accelerate the pace at which effective treatments for disease-causing genetic alterations are developed. According to Dr. Jeff Ross, “the public has a misconception that with improved genomic profiling, everyone’s going to have a target and there’s already an approved drug for their target. The fact is, we can only help 20-30% of patients—like Christine—in a big way. We need to develop better drugs, faster.”

Overcoming both of these challenges is tightly synergistic. Broad testing of patients would make more data available to biopharma companies, accelerating the pace of research and the identification of more patients for clinical trials. Ultimately, that could lead to the development of more effective—and cheaper—targeted drugs. It’s a virtuous cycle, Ross notes: “In the future, more patients who receive genomic diagnostic profiling would have a greater choice of approved treatment options for their specific genetic profile.”

FMI’s partnership with Roche, launched in 2016, is already helping accelerate this process. “Since the partnership began, we’ve expanded FMI services to over 60 countries,” says Josh Lauer, Roche’s Global Head of Personalised Healthcare Market Development. Far from seeing the bio-pharma partners who use FMI data as a commercial threat, Lauer says, Roche recognises that they are vital to “FMI and Roche’s shared goal of accelerating the development of treatments that provide the optimal outcome for every patient diagnosed with advanced cancer.”

This open sourcing of data represents a significant change in how academia and pharma companies have traditionally gone about drug development. Traditionally, “physicians and researchers grew up in a siloed world,” Miller says. “If I make a discovery, I’m going to sit on it and not get it out there until I get a promotion, file for IP, submit for multiple grants, etc.”

Roche, he says, “is leading the global transformation toward a more patient-centric view that doesn’t want to stifle competition, or hold onto anything.”

Cox, the CEO of FMI, shares this view. “What gets me excited is the impact we can make with Roche by building a commercial collaboration where we drive the central standards on new biomarkers, then let the drugs compete on their own merits,” he says.

“The ultimate winners,” Miller says, “will be patients.”

References

1. Ali SM, et al. Comprehensive Genomic Profiling Identifies a Subset of Crizotinib-Responsive ALK-Rearranged Non-Small Cell Lung Cancer Not Detected by Fluorescence in Situ Hybridization. Oncologist. 2016 Jun 21.(6):762-70