The impact of precision medicine on cancer treatment becomes more apparent each day. If you consider the patient experience, you start to see how much has changed already — and how much more is possible.
When I began caring for patients with non-small cell lung cancer (NSCLC) about 30 years ago, the major therapeutic variable was stage of disease at diagnosis. Patients diagnosed at the earliest stages of the disease could be treated relatively effectively with surgery and in some cases chemotherapy and radiation therapy. But more than half of patients did not learn of this dreaded diagnosis until it had reached an advanced stage. Only about one in five of them responded to chemotherapy; on average they lived only seven to eight months thereafter. Whether chemotherapy even helped at all was an area of debate.
Today, there are now 18 approved targeted therapies for patients with advanced lung cancer and more than 80 across all cancers, and hundreds more in development. The targeted treatments indicated by comprehensive genomic tests like FoundationOne®CDx, have produced dramatic improvements for some patients and more modest results for others. For example, in lung cancer, the options include EGFR inhibitors, which are present in about 15% of non-small cell lung cancers and can result in unprecedented outcomes for some patients who may live 5 years or more after diagnosis with metastatic disease.
More recently, “tumor-agnostic” treatments have been developed -- therapies that work based on a molecular feature and independent of the cancer’s anatomic site of origin. Last year the U.S. Food and Drug Administration (FDA) approved the immunotherapy drug pembrolizumab for any solid tumor with either high microsatellite instability or mismatch repair deficiency. Both are genomic biomarkers that indicate increased vulnerability to the drug, and both are also found in lung cancers. Earlier this week, the FDA approved a second tumor-agnostic drug which will benefit a small subset of patients including those with NSCLC identified to have NTRK gene fusions through genomic profiling like FoundationOne CDx.
With the emergence of these genomically targeted treatments, we continue to advance the way we treat cancer -- increasingly not as a disease of any organ, but of the genome. At least 50 percent of cancer treatments in the pipeline will be used in conjunction with some sort of biomarker, usually a genomic change.1 Clinical trials such as the National Cancer Institute’s NCI-MATCH and the American Society of Clinical Oncology’s TAPUR are now often assigning treatment to patients based on genomic changes in their tumors rather than cancer site or type.
Comprehensive genomic profiling is playing a key role in driving the development and success of these therapies and trials, helping to identify advanced cancer patients most likely to benefit from a biomarker-driven therapy based on their genomic profiles. When we analyze a tumor genome in any solid cancer with our FoundationOne CDx test, which comprehensively assesses 324 genes and gene rearrangements, we find that about one in three patients is matched to an already FDA approved targeted therapy. About four out of five patients are matched to a clinical trial of an experimental drug. Patients who are unable to provide a tissue specimen for testing can use FoundationOne® Liquid, which isolates circulating tumor DNA in the bloodstream and tests for genomic alterations in 70 oncogenes to help inform next steps in treatment.
One year ago, the FDA approved FoundationOne CDx across all solid tumors to help inform treatment decisions, and the Centers for Medicare and Medicaid Services approved it for coverage for qualifying patients. This was a meaningful step for patients and reinforces the need for genomic testing, regardless of tumor type. Now the challenge is to improve access and ensure that all patients diagnosed with advanced disease receive comprehensive genomic testing.
Finally, we need to keep making discoveries. With approximately 600 targeted and immunotherapy drugs in late-stage development, the field is determined to find novel targets to fill in the gaps in the therapeutic landscape and make personalized cancer treatment available to a broader spectrum of patients. While there is still work to be done, when there is a match to an effective treatment, the results for the patient can be remarkable. While many experimental therapeutics may fail and some mutant genes may be more challenging to therapeutically target than others, it is unambiguous that for a population of patients matching patients to a treatment increases the chance of benefit as opposed to the sheer empiricism of the classical clinical trials of decades ago.