Conventional cancer clinical studies have produced some extraordinary results in the last decades, causing progress against diseases such as Hodgkin’s lymphoma, which was a near-fatal cancer in adolescents and young adults half a century ago, and breast cancer, which affects to adults mainly.
However, these studies often required recruiting thousands of participants, taking them up to a decade to complete, and costing hundreds of millions of dollars per study. Today, with significant advances in genomics, imaging, bioinformatics, and related disciplines, we are designing smaller, faster, and smarter studies that incorporate the essential principles of precision medicine.
NCI is designing smaller, faster, and smarter studies that incorporate the essential principles of precision medicine.
In the past two years, NCI has launched a series of precision medicine studies, including two studies of lung cancer, Lung-MAP and ALCHEMIST , and NCI-MATCH , which is enrolling patients 18 years of age or older. More with many types of cancer, including non-common cancers. In 2016, the NCI plans to launch a children’s version of MATCH. All three studies adequately illustrate how precision medicine is influencing the way we conduct cancer research,
For example, all three include an initial screening step to determine what mutation (or mutations) may be driving the cancer of an individual patient. Next-generation genomic sequencing and analysis are performed to determine whether a patient’s tumor has one or more mutations that are aligned with approved or investigated targeted therapies.
This screening step is extremely important because it will be used to determine the allocation of treatment to the patient. For example, the ALCHEMIST screening group, which is enrolling patients with early-stage non-small cell lung cancer who has been treated with surgery, will examine 6,000 to 8,000 patients to determine if their tumors have mutations in The ALK or EGFR genes. Patients with ALK mutations will be assigned to a clinical trial that tests for an ALK inhibitor and those with mutations in EGFR will be assigned to a clinical trial that tests for an EGFR inhibitor.
The NCI-MATCH study also requires a new biopsy sample of patient tumors, which helps ensure that sequencing results more accurately reflect tumor characteristics after exposure to conventional treatment, in contrast to samples taken before Treatment.
In addition, because NCI-MATCH has already enrolled nearly 800 patients in only a few months, new inscriptions have been temporarily stopped as study leaders analyze the results of these first patients. This “pause” in the study will allow more mutations and more directed drugs to be added to the study when it restarts, which will allow NCI-MATCH to treat a wider variety of cancers.
Precision medicine studies may also be more agile than most conventional studies. For example, both Lung-MAP and ALCHEMIST are being corrected to include new treatment groups that will assign patients with tumors that lack a mutation to receive immunotherapy drugs.
These precision medical studies present doctors and patients with new issues to consider regarding genetic testing in general. Patients participating in NCI-MATCH and Lung-MAP will be asked about their knowledge and preferences regarding genetic testing. It will be important to determine how well patients understand the differences between germline mutations (mutations that can be transmitted to children) and somatic mutations (mutations that are tumor specific and cannot be transmitted to children).
We are also making important advances in the application of precision medicine in children’s studies. The NCI MATCH Child Study will be conducted nationwide and will be led by the NCI and the Children’s Oncology Group (COG). MATCH Infantil will provide a tremendous opportunity to test molecularly targeted therapies in children and adolescents with recurrent or treatment-resistant solid tumors (including lymphomas) -patients who generally have few additional treatment options.
Although MATCH Infant will be similar in design to the version of NCI-MATCH for adults, there will be some differences. The genetic picture of childhood cancer is much less complex than that of tumors that occur in adults. Childhood tumors contain fewer genetic mutations than adult tumors, and many mutations seen in adult cancers are not detected in childhood cancers. Therefore, the types of substances included in MATCH Infant may differ from those included in NCI-MATCH for adults. When interesting results are seen with a substance in MATCH Infant, that substance can be passed on to other studies for further formulation.
It is important to emphasize that not every cancer clinical trial will require such large-scale changes. Large conventional studies still have a valuable function, for example, to compare therapies that have proven efficacy against a specific cancer or a sub type of cancer, or to test combinations of therapies.
We are already seeing that precision medicine studies offer greater flexibility and efficiency, with the possibility of influencing patient care more quickly. And as we learn more about how to do these studies optimally, we believe we will see even more rapid progress in the coming years.
Social networking event
We encourage you to submit your comments below with your thoughts and questions about precision oncology studies. We also encourage you to read the Annual Plan and Budget Proposal and the remaining blog articles in this series.
And, on January 5 at 1:00 p.m., please join our Google Hangout on Precision Medicine on NCI’s National Clinical Trials Network and use the #Cancer Genomics Outgoing Notification tag. You can find more details on our social networking events page.