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Curious Dr. George: Every year, approximately 600,000 Americans with advanced cancer experience progression of their disease beyond the standards of curative care covered by clinical guidelines. Yet, these guidelines include only a minority of the hundreds of anti-cancer drugs that have been approved by the U.S. Food and Drug Administration (FDA) for marketing, sales, and use. Cancer Commons’ new study enables practicing physicians to include drug sensitivity testing in their choice of such FDA-approved drugs in clinical research. Patterned on the N-of-1 approach, which focuses on a single patient at a time, this is a bold and needed study of an already-available, inexpensive resource. Dr. Pillai, what is this study? How will it work? And how may patients with advanced cancer and their physicians participate?
Prajit Pillai, PhD, MBA: This Cancer Commons N-of-1 study is the first precision medicine study that aims to generate predictive accuracy of functional assays in selecting effective off-guideline treatments. Since the clinical evidence of these assays is severely limited, oncologists are reluctant to use them. This study will add to that body of clinical evidence, and if successful, accelerate the acceptance of these functional assays for treatment selection in clinical practice.
The U.S. National Comprehensive Cancer Network (NCCN) develops the guidelines you described for clinical practice in oncology. If an FDA-approved cancer drug is not recommended in the NCCN guidelines for a particular cancer type, that drug is considered “off-guideline” for that cancer. Off-guideline does not mean the drug has been proven ineffective for that cancer. It means there is no double-blinded, randomized, controlled clinical trial (or other definitive source of clinical validation) that has led the NCCN committee to include that drug in the NCCN guideline for that cancer. A drug may be very effective at treating patients with a particular cancer, but if no clinical trial has been undertaken, then that drug will remain off-guideline for that cancer.
Medical oncologists are extremely reluctant to prescribe their patients off-guideline drugs. A recent study of the Flatiron database of 165,912 cancer patients showed that only 4.4% (1 in 23) received off-guideline drugs. Therefore, a method of guiding oncologists to promising off-guideline drugs, particularly for their advanced cancer patients who are out of treatment options under the NCCN guidelines, could potentially extend the lives of those patients.
In the precision medicine approach to cancer treatment, recommended therapies are selected by matching to a patient’s individual tumor profile. While genomic tests enable selection of targeted therapy, they cannot predict effectiveness of the therapy and have benefited less than 10% of cancer patients. Furthermore, practical challenges with integrating biomarker testing into clinical practice have resulted in most patients not benefiting from precision medicine.
To bring the benefits of precision medicine to more cancer patients, one practical approach is functional precision medicine (FPM), which integrates genomic tumor profiling with drug sensitivity testing (DST). FPM can both validate the genomic-matched findings as well as identify off-guideline drugs when targeted therapy is not feasible. Thus, FPM has the potential to guide oncologists to prescribe patient-specific, off-guideline drugs to advanced cancer patients who are out of treatment options under the NCCN guidelines, potentially extending their lives.
The Cancer Commons study will calculate the predictive accuracy of multiple functional assays (genomic and/or DST) to identify the tests that can be most helpful to patients, and to quantify the potential benefits of these tests.
The study will include 300 advanced cancer patients. The primary objective is to determine the predictive accuracy of selecting off-guideline drugs for advanced cancer patients based on ex vivo DST and genomic profiling. The secondary objective is to compare individual outcomes (response and disease-free survival) in patients treated with DST-guided therapy as compared to non-DST guided (conventional) therapy.
To learn more about the study and how to enroll, I encourage patients and their physicians to visit the Cancer Commons study page and the official study page at ClinicalTrials.gov. Other useful resources related to the study are available on our site for patients, oncologists, and patient navigators.
Dr. Pillai can be reached at prajit.pillai@cancercommons.org.
