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Updates in Cancer for Clinicians UPDATES IN CANCER FOR CLINICIANS WINTER 2014 Progress in Hematologic Cell Transplantation has been associated with lower myeloid leukemia in first remission.1 rates of relapse in acute myeloid With a median follow up of leukemia and better overall surviving patients exceeding five outcomes. These studies utilized years, the non-relapse mortality fixed oral doses of busulfan, of patients receiving IV busulfan which is associated with up to (IV Bu) was only 12 percent at twentyfold variations in plasma one year and 18 percent at five Edward Copelan, MD, (left) levels. Low plasma levels are years, comparable to reports using Chair of the Department of Hematologic associated with graft rejection and allegedly safer reduced intensity Oncology and Blood Disorders leukemia relapse and high levels regimens, and significantly better with toxicity and transplant-related than the TBI group in the study. Belinda Avalos, MD (right) Vice Chair of the Department of mortality. Improved methods Survival and leukemia free survival Hematologic Oncology and Blood of administration, including the (57 percent at five years for IV Disorders intravenous route and dose Bu) were significantly higher and adjustment of busulfan based on late relapse significantly less Initial studies demonstrating plasma levels, represent important frequent with IV Bu compared a cure of acute leukemia with advances which result in much to TBI. A supportive prospective allogeneic transplantation less variation in plasma levels cohort study in patients with were conducted by Nobel and less toxicity. Drs. Copelan various diagnoses, including Laureate E. Donnall Thomas. and Avalos pioneered the use of AML, and shorter follow up and Total body irradiation (TBI) with busulfan preparative regimens an accompanying commentary cyclophosphamide as preparative and advances in its administration. by Richard Champlin, of MD therapy was used. The principal investigators and Anderson, supported and This regimen has remained the lead authors of the plenary paper applauded the results of the standard for 50 years. Regimens in the December 5th issue of study reported by Drs. Copelan substituting busulfan for irradiation Blood, describe for the first time and Avalos. Dr. Champlin labeled have been used at many centers the superiority of intravenous the study the “answer to an because of the relative ease of busulfan compared to TBI in a age-old question.” The results administration and lower rates of study of 1,230 patients from more are viewed by most experts as some delayed effects, including than 100 institutions worldwide practice-changing; in addition hypothyroidism, infertility and who reported to the Center for to ease of administration and certain second malignancies. In International Blood and Marrow fewer complications, non-relapse randomized studies, however, TBI Transplant Research with acute mortality, late relapse, leukemia- CONTINUED ON PAGE 4 LEARN MORE ABOUT LEVINE CANCER INSTITUTE Stereotactic Radiation Incorporating Approaches for Message from The SELECT Palliative Medicine Primary and CarolinasHealthCare.org/UpdatesInCancerV4 the President Lung Cancer Study into Clinical Pathways Oligometastatic Malignancies Message from the President of Levine Cancer Institute system-wide resources, such as that produces a mathematical availability of patient navigation, result of little real importance. This patient support teams, survivorship edition of Updates in Cancer for activities, e-genetic counseling, Clinicians will illustrate how our cancer trials, units to support patients team is approaching the whole at home and improved oncology issue of value in healthcare, as well palliative medicine. In this fashion, as several other important game- Derek Raghavan, MD, PhD we can structure our System’s changing initiatives. I hope you find President, Levine Cancer Institute approach to patient care, and base it to be of interest. Let us know if our decision process on the best you require reprints of any of our available evidence and outcomes. There is no question that every Similarly, we are focusing on value published work. patient, caregiver and health in our academic activities. REFERENCES: professional will increasingly I have participated actively in the 1.Oberlander J and Perreira K: Implementing become involved in the “business” writing of the ASCO Guidelines on Obamacare in a Red State – Dispatch from of healthcare in 2014. It’s a pity, in Choosing Wisely, published in North Carolina. New Engl. J. Med., 2013, one sense, as a great deal of time 369: 2469-2471. will be taken up by this topic, at the Journal of Clinical Oncology4, 5, and in helping to 2.Porter ME, Teisberg EO. Redefining Health the expense of time expended in Care. Boston: Harvard Business School Press, cancer care and research. Some of produce the recent NCI-ASCO 2006. position paper on making trials the current and emerging chaos 3.Raghavan D: Costs of cancer care: is clearly a problem of politics, more accessible to the community Rhetoric, value, and steps forward. Semin. with both sides of the houses of and especially to under-served Oncol., 2013, 40: 659-661. government, both federal and state, populations, published in Journal 4.Schnipper LE, Smith TJ, Raghavan D et 6 failing to execute complete and of Oncology Practice. In addition, al: American Society of Clinical Oncology fiscally justified plans for healthcare our Chair of Solid Tumor Oncology identifies five key opportunities to improve care and reduce costs: the top five list for oncology. coverage and reimbursement. The and Investigational Therapeutics, J. Clin. Oncol., 2012, 30: 1715-1724. schism between federal and state Ed Kim, MD, has recently produced a provocative manuscript on 5.Schnipper LE, Lyman GH, Blayney DW et policies is particularly problematic in al: American Society of Clinical Oncology 1 treatment selection and value in North Carolina. That said, it’s time top five list in oncology. J. Clin. Oncol., 2013, for our nation to focus on costs and the management of lung cancer, 31: 4362-4370. in yet another high-tier journal.7 quality of cancer care, leading to 6.Denicoff AM, McCaskill-Stevens W, Grubbs SS increased value for both patients Not to be outdone, the leaders of et al: The National Cancer Institute-American and the community. I appreciate the our Department of Hematologic Society of Clinical Oncology cancer trial accrual view of Professor Michael Porter, Oncology, Blood Disorders and symposium: summary and recommendations. J. from Harvard School of Business, Bone Marrow Transplantation, Ed Oncol. Pract., 2013, 9: 267-276. who defines “value” as “outcome Copelan, MD, and Belinda Avalos, 7.Kim ES, Neubauer M, Cohn A, et al: divided by cost,” linking two very MD, have summarized their data on Docetaxel or pemetrexed with or without important parameters.2 a new, more cost-effective approach cetuximab in recurrent or progressive non- small-cell lung cancer after platinum-based The whole basis of developing to bone marrow transplantation in 8 therapy: a phase 3, open-label, randomised Levine Cancer Institute has been 1,230 cases in Blood . trial. Lancet Oncol, 2013,14:1326-1336. If you asked any within our team, to improve value – as outlined in 8.Copelan EA, Hamilton BK, Avalos B my recent editorial in “Seminars our focus remains quality and et al: Better leukemia-free and overall in Oncology”3, our approach has consistency, as supported by our survival in AML in first remission following been to use electronically driven recent score of the top 1 percent in cyclophosphamide in combination with pathways to rationalize and refine the Press Ganey survey. However, it busulfan compared with TBI. Blood, 2013, care, focusing on using the most is increasingly clear that our nation 122: 3863-3870. effective anti-cancer agents, and simply cannot afford the current choosing less toxic options when the costs of healthcare, and we all need Sincerely, efficacies of different approaches to focus on the provision of value are the same. Where approaches in addition to volume. We need to are equivalent in anti-cancer efficacy look at the reported advances and and toxicity, our intent is to move ensure that they are real, and of true We welcome your feedback at [email protected] to a cost-based algorithm. We also clinical relevance, and not merely and look forward to bringing you more news are improving value by developing the products of a statistical exercise in the future! 2 I UPDATES IN CANCER FOR CLINICIANS A PUBLICATION OF CAROLINAS HEALTHCARE SYSTEM The SELECT Lung Cancer Study: What did we learn about cetuximab and chemotherapy in second line treatment? antibody targeting EGFR, is Though these results were FDA approved for the treatment disappointing, definitive of head and neck cancer and information will be gained colorectal cancer. Kras has been from a current intergroup identified as a marker of resistance study, Southwest Oncology against cetuximab in patients with Group (SWOG) S0819, testing colon cancer; however, no markers cetuximab with chemotherapy have been identified in head and and bevacizumab. This is currently Edward S. Kim, MD Chair of the Department of Solid Tumor neck cancer. the largest front-line metastatic Oncology and Investigational Therapeutics In lung cancer, cetuximab has lung cancer study open to accrual been studied extensively. The (currently more than 1,000 patients FLEX study, a frontline advanced on study) and was based on Targeted therapies have non-small cell lung cancer (NSCLC) SWOG S0536, a single-arm, phase become incorporated into our trial combined with chemotherapy, II study with promising efficacy daily practice and management showed a statistically significant using carboplatin, paclitaxel, of patients with lung cancer. The improvement in overall survival bevacizumab, and cetuximab discoveries of epidermal growth (OS), however, this translated into (OS: 15 months, RR: 56 percent).4 factor receptor (EGFR) mutations only a five week difference.1 The Biomarker analyses are a co- and anaplastic lymphoma drug was not approved based primary endpoint with overall kinase (ALK) translocations on this information.
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