ASCO's TAPUR STUDY FOR PRECISION MEDICINE

Treatment of advanced-stage cancer is evolving—the days when chemotherapy, radiation therapy, and surgery were the only tools to fight cancer are fading away. As our knowledge of the human genome has grown, so has our knowledge of the molecular pathways involved in the development and spread of cancer. Physicians are relying less on the physical location of the tumor and more on the tumor's molecular features to guide treatment decisions. Precision medicine—tailoring therapy to individual people's genes, environments, and lifestyles—is here to stay and playing an increasing role in cancer treatment.

In fact, as a nation we are investing millions of dollars across many organizations, including the National Institutes of Health and the US Food and Drug Administration (FDA), to continue developing precision medicine through programs such as the President's Precision Medicine Initiative, Vice President Biden's national Cancer Moonshot, and the National Cancer Institute's Molecular Analysis for Therapy Choice (NCI-MATCH).

In 2015, an unprecedented six drugs were FDA approved for patients with lung cancer, four of which were approved with accompanying companion diagnostic tests: pembrolizumab, osimertinib, gefitinib, and alectinib. This has led to an increased opportunity for lung cancer patients to be treated in a more personalized manner; it has also led clinicians to order larger molecular panels of biomarkers as part of a standard cancer workup. Increasingly, we are observing the same molecular aberrations across multiple tumor types but with no drug approved within that specific tumor.

The American Society of Clinical Oncology (ASCO) is heavily invested in the growth of precision medicine. ASCO's first clinical research study, the Targeted Agent and Profiling Utilization Registry (TAPUR) study, opened recently at four sites in the United States including Carolinas HealthCare System's Levine Cancer Institute, Cancer Research Consortium of West Michigan, Michigan Cancer Research Consortium, and the University of Michigan. The study's principal investigator is ASCO's chief medical officer, Richard L. Schilsky, MD.

Genomic testing is widely available and can reveal molecular abnormalities that could be targeted with available cancer drugs. However, if that drug is not FDA approved for the patient's specific cancer type, as is often the case, physicians may have a difficult time getting coverage for off-label drug use. ASCO's TAPUR trial is a unique approach to evaluating the efficacy of targeted therapies prescribed off-label while making these drugs accessible to patients. TAPUR will collect information on the outcomes of patients who are treated with off-label drugs, information that is not currently captured. As of right now, 17 drugs are planned for inclusion in the TAPUR study, and at least five major pharmaceutical companies will participate (AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Genentech, and Pfizer, with additional companies to be added).

TAPUR's main goal is to evaluate the efficacy and safety of the drugs included in the study. Specifically, the study's primary endpoint is to evaluate objective tumor response or stable disease at 16 weeks after treatment initiation. TAPUR will also examine progression-free survival, overall survival, duration of treatment on study, and treatment-related high-grade and serious adverse events and will also catalogue the commercially available genomic tests used by participating oncologists.

Patients who are eligible for TAPUR must have advanced solid tumors, multiple myeloma, or B-cell non-Hodgkin lymphoma. Patients must also have previously undergone genomic testing that reveals a genomic variation that is part of the TAPUR protocol. Physicians and their patients are free to choose which type of genomic test would be appropriate and can choose from tests using tumor tissue or blood.

The TAPUR study eligibility criteria are broad, reflecting the type of patients seen in clinical practice. This is in contrast to most clinical studies, where eligibility criteria are strict, creating a clinical trial population that is not truly reflective of the patients treated in the real-world setting. This is just one strength of the TAPUR study.

Another positive aspect of the TAPUR study is that patients are not randomly assigned. Any patient who is enrolled on TAPUR and whose tumor contains an actionable genomic variant that matches a particular drug will receive the matched drug at no cost and will continue to receive the drug for as long as they continue to benefit. If a patient has a genomic variation that does not match to a TAPUR study drug, or the treating oncologist is uncertain about a patient's test results, the treating oncologist may request review from the TAPUR study's Molecular Tumor Board (MTB). The MTB could provide information on alternative clinical trials or could suggest off-label treatment with a non-TAPUR drug if the patient is ultimately not eligible for TAPUR.

As the practice of oncology becomes increasingly more complex, patients are benefiting from the approval of new drugs that target specific molecular aberrations in their tumor. Larger amounts of molecular information are desired in order to discover new potential druggable pathways as well as identify existing drug targets in other tumor types. Studies like ASCO's TAPUR trial are helping to collect and assemble the information necessary to formulate new research ideas, while also addressing the challenges of current clinical practice.