Simon B. Zeichner

Improved clinical outcomes associated with vitamin D supplementation during adjuvant chemotherapy in patients with HER2+ nonmetastatic breast cancer.

BACKGROUNDnVitamin D (VD) supplementation has pleiotropic effects that extend beyond their impact on bone health,xa0including the disruption of downstream VD receptor signaling and human epidermal growth factor receptor 2 (HER2) signaling through the ErbB2/AKT/ERK pathway. In the present study, we examined our institutional experience with patients having nonmetastatic HER2-positive (HER(+)) breast cancer and hypothesized that those patients who received VD supplementation during neoadjuvant chemotherapy would have improved long-term outcomes.nnnPATIENTS AND METHODSnWe performed a retrospective review of all patients (nxa0= 308) given trastuzumab-based chemotherapy between 2006 and 2012 at the University of Miami/Sylvester Comprehensive Cancer Center (UM/SCCC). We identified 2 groups of patients for comparison-those who received VD supplementation during neoadjuvant chemotherapy (nxa0=xa0134) and those who did not (nxa0= 112). Univariate and multivariate Cox proportional hazard regression models were fitted to overall survival (OS) and disease-free survival (DFS).nnnRESULTSnMore than half of the patients received VDxa0during neoadjuvant chemotherapy (54.5%), with 60% receiving a dosexa0< 10,000 units/wk and 33.3% having axa0VDxa0deficiency at the start of therapy. In our final multivariate model, VD use was associated with improved DFSxa0(hazardxa0ratio [HR], 0.36; 95% confidence interval [CI], 0.15-0.88; Pxa0= .026], whereas larger tumor size was associated with worse DFS (HR, 3.52; 95% CI, 1.06-11.66; Pxa0= .04). There were no differences in OS based on any of the categories, including VD use, tumor size, number of metastatic lymph nodes, age at diagnosis, or lymphovascular invasion (LVI).nnnCONCLUSIONnVD supplementation in patients with nonmetastatic HER2(+) breast cancer is associated with improved DFS.

A Review of Systemic Treatment in Metastatic Triple-Negative Breast Cancer

Patients with breast cancer along with metastatic estrogen and progesterone receptor (ER/PR)- and human epidermal growth factor receptor 2 (HER2)-negative tumors are referred to as having metastatic triple-negative breast cancer (mTNBC) disease. Although there have been many new treatment options approved by the Food and Drug Administration for ER/PR-positive and Her2/neu-amplified metastatic breast cancer, relatively few new agents have been approved for patients with mTNBC. There have been several head-to-head chemotherapy trials performed within the metastatic setting, and much of what is applied in clinical practice is extrapolated from chemotherapy trials in the adjuvant setting, with taxanes and anthracyclines incorporated early on in the patients treatment course. Select synergistic combinations can produce faster and more significant response rates compared with monotherapy and are typically used in the setting of visceral threat or symptomatic disease. Preclinical studies have implicated other possible targets and mechanisms in mTNBC. Ongoing clinical trials are underway assessing new chemotherapeutic strategies and agents, including targeted therapy and immunotherapy. In this review, we evaluate the standard systemic and future treatment options in mTNBC.

Cost-Effectiveness of Immune Checkpoint Inhibition in BRAF Wild-Type Advanced Melanoma

Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17%. Randomized controlled trials of recent US Food and Drug Administration-approved immune checkpoint inhibitors-pembrolizumab (PEM), nivolumab (NIVO), and ipilumumab (IPI)-demonstrate improved patient outcomes, but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear. To inform policy makers about the value of these treatments, we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma. Materials and Methods We developed Markov models by using a US-payer perspective and lifetime horizon to estimate costs (2016 US

Survival of patients with de-novo metastatic breast cancer: analysis of data from a large breast cancer-specific private practice, a university-based cancer center and review of the literature

) and quality-adjusted life years (QALYs) for treatment sequences with first-line NIVO, IPI, NIVO + IPI, PEM every 2 weeks, and PEM every 3 weeks. Health states were defined for initial treatment, first and second progression, and death. Rates for drug discontinuation, frequency of adverse events, disease progression, and death obtained from randomized phase III trials were used to determine the likelihood of transition between states. Deterministic and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. Results PEM every 3 weeks followed by second-line IPI was both more effective and less costly than dacarbazine followed by IPI then NIVO, or IPI followed by NIVO. Compared with the first-line dacarbazine treatment strategy, NIVO followed by IPI produced an incremental cost effectiveness ratio of

Secondary Adult Acute Myeloid Leukemia: a Review of Our Evolving Understanding of a Complex Disease Process

90,871/QALY, and first-line NIVO + IPI followed by carboplatin plus paclitaxel chemotherapy produced an incremental cost effectiveness ratio of

Cost-effectiveness analysis of 1st through 3rd line sequential targeted therapy in HER2-positive metastatic breast cancer in the United States

198,867/QALY. Conclusion For patients with treatment-naive BRAF wild-type advanced melanoma, first-line PEM every 3 weeks followed by second-line IPI or first-line NIVO followed by second-line IPI are the most cost-effective, immune-based treatment strategies for metastatic melanoma.

Cost-effectiveness of precision medicine in gastrointestinal stromal tumor and gastric adenocarcinoma

AbstractApproximately 6xa0% of patients with breast cancer are diagnosed with de-novo distant metastases. We set out to look at two cohorts of patients seen at breast cancer-specific practices, compare the results to other reports and larger databases, and see how advances in treatment have impacted overall survival (OS). The records from a large breast cancer oncology private practice and a second data set from the University of Miami/Sylvester Comprehensive Cancer Center (UM/SCCC) tumor database were, retrospectively, reviewed to identify patients with de-novo metastases. We included those patients identified to have metastatic disease within 3xa0months of diagnosis of a breast primary cancer. Patients diagnosed between 1996 and 2006 were chosen for our study population. The OS for the private practice was 41.0xa0months (46.0 for ER positive and 26.0 for ER negative) and 36.0xa0months for UM/SCCC (52xa0months for ER positive and 36xa0months for ER negative). ER negativity and CNS- or visceral-dominant disease were associated with a significantly worse prognosis within the private practice. Dominant site was associated with a significantly worse prognosis within the UM/SCCC database but with a trend also for ER negativity. Age and ethnicity did not contribute significantly to the survival of patients within either cohort. The median survival in both cohorts and most other reported series was larger than that seen in the surveillance, epidemiology, and end results program and the National Cancer Database. The median OS among patients with de-novo metastatic breast cancer treated within two breast-specific oncology practices was over 3xa0years, which appears better than larger, more inclusive databases and publications from earlier decades.n

Allogeneic Hematopoietic Cell Transplantation for Adult T Cell Acute Lymphoblastic Leukemia

Opinion StatementSecondary AML (s-AML) encompasses AML evolving from myelodysplasia (AML-MDS) and treatment-related AML (t-AML) after exposure to chemotherapy, radiation, or environmental toxins. S-AML has traditionally been considered a devastating disease, affecting a vulnerable population of heavily pretreated, older adults. A limited understanding of disease pathogenesis/heterogeneity and lack of effective treatments have hampered overall improvements in patient outcomes. With the recent understanding that the secondary nature of sAML does not by itself incur a poor prognosis and incorporation of cytogenetics and molecular genetics into patient care and the advancement of treatment, including improved supportive care, novel chemotherapeutics agents, and nonmyeloablative conditioning regimens as part of allogeneic hematopoietic cell transplantation (HCT), modest gains in survival and quality of life are beginning to be seen among patients with s-AML.

Defining the Survival Benchmark for Breast Cancer Patients with Systemic Relapse

AbstractPurposenBased on available phase III trial data, we performed a cost-effectiveness analysis of different treatment strategies that can be used in patients with newly diagnosed HER2-positive metastatic breast cancer (mBC).Patients and methodsWe constructed a Markov model to assess the cost-effectiveness of four different HER2 targeted treatment sequences in patients with HER2-positive mBC treated in the U.S. The model followed patients weekly over their remaining life expectancies. Health states considered were progression-free survival (PFS) 1st to 3rd lines, and death. Transitional probabilities were based on published phase III trials. Cost data (2015 US dollars) were captured from the U.S. Centers for Medicare and Medicaid Services (CMS) drug payment table and physician fee schedule. Health utility data were extracted from published studies. The outcomes considered were PFS, OS, costs, QALYs, the incremental cost per QALY gained ratio, and the net monetary benefit. Deterministic and probabilistic sensitivity analysesxa0assessed the uncertainty around key model parameters and their joint impact on the base-case results.ResultsThe combination of trastuzumab, pertuzumab, and docetaxel (THP) as first-line therapy, trastuzumab emtansine (T-DM1) as second-line therapy, and lapatinib/capecitabine third-line resulted in 1.81 QALYs, at a cost of

External Validation of Generic and Cancer-Specific Risk Stratification Tools in Patients With Pulmonary Embolism and Active Cancer

335,231.35. The combination of trastuzumab/docetaxel as first line without subsequent T-DM1 or pertuzumab yielded 1.41 QALYs, at a cost of