Chairman and Principal Investigator, National Surgical Adjuvant Breast and Bowel Project (NSABP)
Professor and Chairman of Human Oncology
Drexel University School of Medicine
Project 1: On behalf of National Surgical Adjuvant Breast and Bowel Project
Co-Investigators: Matthew J. Ellis, MD, PhD, Washington University School of Medicine, St. Louis, MO and Samuel A. Jacobs, MD, University of Pittsburgh Cancer Institute, Pittsburgh, PA
Technologies for unbiased discovery of the events underlying cancer are improving at a rapid pace. It is, therefore, critically important that scientists evolve their approaches to clinical investigation to match the demands and opportunities that the integrated studies of cancer DNA, RNA, and proteins - collectively referred to as "cancer 'omics" present.
The ready availability of tissue from patients receiving systemic treatment before surgery (neoadjuvant therapy) for breast cancer is of central importance to the 'omics field as serial sample acquisition can be reliably attempted before and after the initiation of therapy. Several National Cancer Institute Clinical Proteomic Tumor Analysis Consortium centers have, therefore, developed a collaboration with the National Surgical Adjuvant Breast and Bowel Project (NSABP) to determine the feasibility of conducting a deep proteogenomic analysis of samples from the phase II randomized clinical trial evaluating neoadjuvant chemotherapy regimens with weekly paclitaxel or eribulin followed by doxorubicin and cyclophosphamide in women with locally advanced HER2 negative breast cancer. The long-term objective of this study is to develop standard operating procedures that will allow integrated cancer 'omics from all neoadjuvant breast cancer protocols conducted by the NSABP, and indeed, by all cooperative groups. In 2013-2014, the NSABP will continue to work on this novel discovery protocol. All pre-activation activities for Discovery Protocol 1 ("DP-1"), including developing the database needed for operation of the protocol, have been completed. BCRF funding is supporting uninterrupted patient accrual and collection of specimens through the continuation of the project.
Project 2: On behalf of National Surgical Adjuvant Breast and Bowel Project
Co-Investigator: Patricia A. Ganz, MD, University of California, Los Angeles, CA
Also, BCRF funding has been been applied towards a second NSABP study led by grantee Patricia Ganz, MD (University of California, Los Angeles). Clinical trials focus primarily on the efficacy of a treatment—does it prolong survival or disease-free survival? The final outcomes and interpretation of clinical trials are often enhanced through collection of patient reported outcomes (PROs) related to symptoms and quality of life that reflect the experience of the patients receiving the therapy, especially when one treatment arm is expected to be substantially more toxic than the other.
A second kind of outcome study, less frequently included, is a cost of care study; however, such research is equally important for the interpretation of how best to implement the results of clinical trials in breast cancer once a trial has been completed. As new targeted therapies demonstrate benefit in advanced metastatic breast cancer they are being moved into the adjuvant treatment of breast cancer. These new agents bring substantial promise for higher cure rates when added to standard adjuvant therapy, but can also add substantially to the cost of care. The increased cost of care includes the drug itself, which may be considerable, along with additional costs that can be incurred due to increased toxicities resulting in additional office visits, prescribed medications to manage toxicities, as well as increased hospitalizations. BCRF funds in 2012-2013 allowed the NSABP to amend a major treatment protocol studying the new drug everolimus (Affinitor®) to add a cost of care study to a quality of life component. Without this funding and opportunity to add this component, investigators would have missed the opportunity to learn about whether the drug adds to the burden of health care utilization and costs for women who receive it. The revision of the trial has been completed, and it will be launched shortly. This research aims to provide a complete picture of the benefits and risks of this new therapy for breast cancer.
Project 1: NSABP has activated Discovery Protocol 1 ("DP-1"), and the researchers report that each of the five participating NSABP Member sites, of which all are major universities and health systems, have activated the study at their institutions. To date, Washington University has enrolled one patient. Study Marketing - DP-1 was presented at two meetings of NSABP investigators in Chicago (October) and San Antonio (December). Also, in keeping with plans to build awareness of this novel study at the site level, NSABP has worked closely with each site during its local activation to identify a surgeon and a nurse coordinator, whose responsibility it is to work as a team to identify DP-1 eligible patients at the sites, explain the protocol and consent the patient. In addition, the local study activation process on the NSABP Foundation website contains educational information geared to key study personnel at participating sites. The major focus for the remainder of BCRF support Year 2 is to enroll and collect specimens from as many of the 50 patient sample size as possible. The projection for Year 2 was to accrue between 3 and 7 patients, and this remains achievable. While the research team has made substantial progress in bringing this novel Discovery Protocol to its current state, each step along the way has presented special challenges in the timing of its completion. Currently, a meeting of PIs from participating sites is scheduled for late January to address patient enrollment. Further discussion is planned at the NRG Oncology meeting in February. The plan is now to focus on patient enrollment and to reassess project progress in the spring.
Project 2: BCRF funding has permitted the researchers to collect data on additional services that may occur alongside the use of a new targeted breast cancer treatment that is being evaluated in a recently launched adjuvant treatment trial. This will facilitate an examination of both the benefits (extended survival), quality of life impact, and value (costs) of this targeted treatment at the end of the trial. Without the real time collection of data concerning side effects that may require additional tests and medical treatments, we would not be able to estimate the additional cost of this new treatment. The increased cost of care includes the drug itself, which is considerable, along with additional costs that can be incurred due to increased toxicities resulting in additional office visits, prescribed medications to manage toxicities, as well as increased hospitalizations. The clinical trial opening was delayed until the fall of 2013. As of mid-January 2014, 25 patients have been registered on the trial with 1 patient in the substudy for quality of life and cost component. The researchers expect the monthly accrual to the trial to accelerate as more clinical sites open the trial.
Norman Wolmark, MD is Chairman and Principal Investigator of the National Surgical Adjuvant Breast and Bowel Project (NSABP), which is primarily funded by the National Cancer Institute and is based in Pittsburgh, Pennsylvania. He is also Professor and Chairman of Human Oncology, Drexel University School of Medicine.
Dr. Wolmark gained his MD at McGill University, Montreal, Canada and he subsequently completed his residency at the University of Pittsburgh. Dr. Wolmark was then appointed to the position of Cancer Expert at the Surgery Branch of the National Cancer Institute, Bethesda, Maryland. Dr. Wolmark is a member of numerous professional societies, including the American Society of Clinical Oncology (ASCO), the American Association for Cancer Research (AACR), and the American Surgical Association (ASA).
He is a reviewer for the journal of Clinical Oncology and the New England Journal of Medicine and an editorial board member of the Journal of Women's Cancer, and Clinical Breast Cancer. He also serves on numerous boards and as an advisor to oncology programs, societies and institutes throughout the United States, Europe, and Asia.