Shumei Kato, Vivek Subbiah, and Razelle Kurzrock
Razelle Kurzrock, Robert Goldberg, Alice C. Ceacareanu, and Zachary A. P. Wintrob
Background: It is sometimes suggested that newly-approved cancer treatments have only marginal effectiveness, which raises questions concerning their cost-vs-benefit ratio. Such concerns appear at odds with the lower cancer-related hospitalization rate and improved survival. However, such cost-effectiveness analyses rely on population-based averages obtained from the analysis of clinical trial data. By failing to analyze data from longitudinal datasets, such assessments are unable to account for real-world patient conditions and treatment patterns in evaluating clinical and cost-effectiveness. Longitudinally surveyed clinical data has the potential to objectively reveal any association between patient outcomes and new cancer treatment utilization. Methods: We investigated the effect of being prescribed a higher proportion of new oncology drugs on quality of life, medical services use, and productivity measures as reported by the Medical Expenditure Panel Survey (MEPS, 1996–2015). General linear models with Taylor series variance estimation were applied. New oncology drugs were defined as cancer treatments marketed after the year 2000. Included subjects (N=16,677) had a solid or hematologic malignancy diagnosis (CCCodex 11–47) and available prescription data. Individual age and employment status were accounted for as covariates. All analyses were performed using SAS version 9.4 (Cary, NC). Results: Unadjusted regression data show that individuals using newer oncology treatments missed on average 2.5 (±0.3 SE) fewer days of work or school per year as compared to patients using older drugs (43% improved productivity, P<.0001). The effect persisted even after adjusting for the magnitude of the effect (P<.0001). Accounting for age, the use of newer drugs was, on average, associated with ∼35% fewer missed work or school days. Cancer patients using newer treatments had 0.06 (±0.01 SE) fewer hospital admissions/year compared to patients using older treatments (P<.0001) and spent less time in the emergency room (P<.0411) with ∼45% fewer hospitalizations. Patients using newer medicines also had fewer health-related visits (P<.0001). Conclusion: Analysis of longitudinal real-world evidence gives a more comprehensive and reliable view of the clinical and economic impact of new oncology treatments. Our data suggests significant reductions in lost work/school days, hospitalizations, and use of medical services in general.
Apostolia M. Tsimberidou, Alexandra M. Adamopoulos, Yang Ye, Sarina Piha-Paul, Filip Janku, Siqing Fu, David Hong, Gerald S. Falchook, Aung Naing, Jennifer Wheler, Adoneca Fortier, Razelle Kurzrock, and Kenneth R. Hess
Bendamustine, a cytotoxic alkylating agent, has shown promising results in solid tumors. An investigator-initiated phase I clinical trial of the anti-vascular endothelial growth factor agent bevacizumab and bendamustine was conducted in patients with advanced cancer, because the 2 drugs have different mechanisms of antitumor activity and nonoverlapping toxicity. Patients were treated with escalating doses of intravenous bendamustine (70, 80, 90, and 100 mg/m2; days 1 and 2) and intravenous bevacizumab (10 mg/kg; days 1 and 15). A conventional “3 + 3” study design was used. Forty-two patients were treated: 23 women and 19 men. The median age was 60 years. Patients had received a median of 4 prior therapies (range, 1-10). The most common cancer types were colorectal (n=9), head and neck (n= 8), non-small cell lung (n=6), and breast (n=5). Overall, 117 cycles were administered (median per patient, 2; range, 1-8). No dose-limiting toxicities were noted during the escalation phase. Therefore, the highest dose (level 4) of bendamustine (100 mg/m2) was used in the expansion phase. The most common toxicities were fatigue (n=22), nausea (n=14), anorexia (n=9), and thrombocytopenia (n=7). Of 38 patients who were evaluable for response, 23 (61%) had stable disease, including 2 (5.2%) who had stable disease for 6 months or more (1 with adenoid cystic carcinoma and 1 with non-small cell lung cancer). This regimen of bendamustine (100 mg/m2) and bevacizumab (10 mg/kg) was well tolerated and yielded disease stabilization in selected heavily pretreated patients with advanced cancer.
Jacob J. Adashek, Shumei Kato, Rahul Parulkar, Christopher W. Szeto, J. Zachary Sanborn, Charles J. Vaske, Stephen C. Benz, Sandeep K. Reddy, and Razelle Kurzrock
Razelle Kurzrock, A. Dimitrios Colevas, Anthony Olszanski, Wallace Akerley, Carlos L. Arteaga, William E. Carson III, Jeffrey W. Clark, John F. DiPersio, David S. Ettinger, Robert J. Morgan Jr, Lee S. Schwartzberg, Alan P. Venook, Christopher D. Gocke, Jonathan Tait, and F. Marc Stewart
Background: With advances such as next-generation sequencing (NGS) increasing understanding of the basis of cancer and its response to treatment, NCCN believes it is important to understand how molecular profiling/diagnostic testing is being performed and used at NCCN Member Institutions and their community affiliates. Methods: The NCCN Oncology Research Program's Investigator Steering Committee and the NCCN Best Practices Committee gathered baseline information on the use of cancer-related molecular testing at NCCN Member Institutions and community members of the NCCN Affiliate Research Consortium through 2 separate surveys distributed in December 2013 and September 2014, respectively. Results: A total of 24 NCCN Member Institutions and 8 affiliate sites provided quantitative and qualitative data. In the context of these surveys, “molecular profiling/diagnostics” was defined as a panel of at least 10 genes examined as a diagnostic DNA test in a Clinical Laboratory Improvement Amendments (CLIA)–certified laboratory. Conclusions: Results indicated that molecular profiling/diagnostics are used at 100% of survey respondents' institutions to make patient care decisions. However, challenges relating to reimbursement, lack of data regarding actionable targets and targeted therapies, and access to drugs on or off clinical trials were cited as barriers to integration of molecular profiling into patient care. Frameworks for using molecular diagnostic results based on levels of evidence, alongside continued research into the predictive value of biomarkers and targeted therapies, are recommended to advance understanding of the role of genomic biomarkers. Greater evidence and consensus regarding the clinical and cost-effectiveness of molecular profiling may lead to broader insurance coverage and increased integration into patient care.
Alan P. Venook, Maria E. Arcila, Al B. Benson III, Donald A. Berry, David Ross Camidge, Robert W. Carlson, Toni K. Choueiri, Valerie Guild, Gregory P. Kalemkerian, Razelle Kurzrock, Christine M. Lovly, Amy E. McKee, Robert J. Morgan, Anthony J. Olszanski, Mary W. Redman, Vered Stearns, Joan McClure, and Marian L. Birkeland
Defining treatment-susceptible or -resistant populations of patients with cancer through the use of genetically defined biomarkers has revolutionized cancer care in recent years for some disease/patient groups. Research continues to show that histologically defined diseases are diverse in their expression of unique mutations or other genetic alterations, however, which presents opportunities for the development of personalized cancer treatments, but increased difficulty in testing these therapies, because potential patient populations are divided into ever smaller numbers. To address some of the growing challenges in biomarker development and clinical trial design, NCCN assembled a group of experts across specialties and solid tumor disease types to begin to define the problems and to consider alternate ways of designing clinical trials in the era of multiple biomarkers and targeted therapies. Results from that discussion are presented, focusing on issues of clinical trial design from the perspective of statisticians, clinical researchers, regulators, pathologists, and information developers.