Today, a new paradigm for cancer care may be emerging, where treatments are identified based on the unique genetic makeup of an individual’s tumour, regardless of where it first originated.
Lung Cancer. Breast Cancer. Skin Cancer. Tumour-agnostic. Rather than recommending treatments solely based on whether an individual has a specific type of cancer, we are now looking at the disease at the molecular level to understand the best way to treat it. These “tumour-agnostic” therapies are beginning to show promise in clinical settings, helping patients across a range of rare and hard-to-treat cancers.
Tumour-agnostic approaches to cancer treatment are part of a broader trend in personalised healthcare — a field of research that has rapidly expanded in recent years, due in part to advances in genomic sequencing technologies.
"We’ve come a long way in a short time and here’s what’s changed," says Prof Hans Prenen, Deputy Head of the Oncology Department and Director of Clinical Trial Management at the University Hospital Antwerp. “Huge advances in how we test genes and mutations in tumours mean that we now better understand what drives them, what makes them grow. Knowing about these genetic drivers means we can develop precision treatments that specifically target them — this is incredibly exciting.”
This breakthrough in understanding what drives the growth of many cancers means that patients with rare genetic abnormalities — who previously had very limited or no treatment options — now have hope. By bringing together sophisticated genomic testing with precision tumour-agnostic medicines, we’re able to provide new treatment approaches for patients. For example, we already know that some rare gene fusions such as NTRK and ROS1 are present in a broad range of tumours, including those of the head and neck, salivary gland, bladder and lung, to name a few.
“These are patients for whom a cancer diagnosis would have been completely different 10, 12 or 15 years ago, but now it’s a whole new ball game,” says Dr Alex Spira, Director, Virginia Cancer Specialists Research Institute. “Now there are a lot of therapies that are targeted for specific mutations and DNA changes. We can treat people on an individual basis rather than just doing the same thing for everybody.
But in order for this paradigm shift to occur, the entire health ecosystem must evolve as rapidly as the scientific advances that are enabling it, says Edward Abrahams, President of the Personalised Medicine Coalition. “The number one obstacle to paradigm change is the lack of understanding among the multiple stakeholders involved,” he says. “We have to understand where everybody else is coming from to make the medical system, which is chaotic no matter where it is, coalesce.”
This is one of the key messages of a new
“Increased awareness is the foundation for getting all the other pieces in place to ensure systems can support the introduction of tumour-agnostic medicines,” says A.T. Kearney partner, Michael Thomas.
“The management of cancer has always been handled tumour-type by tumour-type,” Thomas says. “Whether that’s in terms of how we license products, how we deliver care, how we specialise as oncologists or how we set up our patient associations, there is a very established way of doing things. If we want to get these innovations into the hands of patients who need them, we will need to have a more flexible approach.”
Things are heading in the right direction. Regulatory and health technology assessment bodies around the world that review, approve and reimburse medicines are working hard to find ways to evaluate innovative therapies. Organisations such as the American Food and Drug Administration (FDA) and the British National Institute for Health and Care Excellence (NICE)*, for instance, have shown a willingness to accept novel trial designs — such as basket studies, which enroll patients for treatments based on the biology of their tumour, not their tumour type – to support innovative therapies.
However, there are still significant discussions going on among regulators and health technology assessment bodies on how to evaluate tumour-agnostic treatments. The more rare the disease and the more targeted the treatment is, the more difficult it is to generate large sets of data from clinical trials. According to the report, this makes it crucial to explore new evaluation methodologies and pathways for these treatments.
Newer approaches to drug approvals, especially where rare cancers are concerned, will also require the development of additional technologies and processes for data collection and review. Innovative technologies such as patient apps or electronic patient registries, the creation of impressive genomic databases that provide new insights, and partnerships with oncology data experts like Flatiron Health are all improving our ability to collect and analyse data. These will provide real-world evidence that can support medicine approvals, and provide insights into how a patient’s cancer could potentially evolve and recur, informing future treatment approaches.
The report also recommends that next-generation sequencing (NGS) tests become a standard part of cancer treatment protocols. One of the most important transformations is already beginning to occur. Precision oncology is entering the mainstream of clinical practice, with clinicians using genomic profiling to identify targetable alterations and tailored treatments — including tumour-agnostic therapies — for their patients.
While most health systems acknowledge the need to roll out high-quality NGS — with some countries making firm commitments to do so — access to, and reimbursement for, such testing remains limited.
“NGS looks at many different genes through fancy algorithms, DNA sequencing, and very intensive computer programming to figure out what’s causing a patient’s cancer to grow,” says Spira. “It’s essential to truly understand the individual nature of each person’s disease, so we can develop more personalised treatments.”
“While it will take time for all the pieces to come together, the potential of tumour-agnostic therapies ‘is completely transformative’,” says Prenen.
“The science is continuing to evolve at a rapid pace, and is giving us more hope than ever of tackling each individual’s cancer,” he says. “Now it’s the duty of all stakeholders to come together to understand what this means for the future of cancer care, and how we can accommodate such innovation within the current systems. If we can do this, we will be on the cusp of something very special.”
*NICE is an independent organisation, set up by the Government in 1999, to decide which drugs and treatments are available on the National Health Service (NHS) in England.