The ASCEND-NHQ randomized trial found positive effects of daprodustat on hemoglobin and quality of life in patients with non-dialysis chronic kidney disease.

The ASCEND-NHQ trial evaluated the effects of daprodustat on hemoglobin and the Medical Outcomes Study 36-item Short Form Survey (SF-36) Vitality score (fatigue) in a multicenter, randomized, double-blind, placebo-controlled trial. Adults with chronic kidney disease (CKD) stages 3-5, hemoglobin 8.5-10.0 g/dl, transferrin saturation 15% or more, and ferritin 50 ng/ml or more without recent erythropoiesis-stimulating agent use were randomized (1:1) to oral daprodustat or placebo to achieve and maintain target hemoglobin of 11-12 g/dl over 28 weeks. The primary endpoint was the mean change in hemoglobin between baseline and the evaluation period (Weeks 24-28). Principal secondary endpoints were proportion of participants with a 1 g/dl or more increase in hemoglobin and mean change in the Vitality score between baseline and Week 28. Outcome superiority was tested (1-sided alpha level of 0.025). Overall, 614 participants with non-dialysis-dependent CKD were randomized. The adjusted mean change in hemoglobin from baseline to the evaluation period was greater with daprodustat (1.58 vs 0.19 g/dl). The adjusted mean treatment difference (AMD) was significant at 1.40 g/dl (95% confidence interval 1.23, 1.56). A significantly greater proportion of participants receiving daprodustat showed a 1 g/dl or greater increase in hemoglobin from baseline (77% vs 18%). The mean SF-36 Vitality score increased by 7.3 and 1.9 points with daprodustat and placebo, respectively; a clinically and statistically significant 5.4 point Week 28 AMD increase. Adverse event rates were similar (69% vs 71%); relative risk 0.98, (95% confidence interval 0.88, 1.09). Thus, in participants with CKD stages 3-5, daprodustat resulted in a significant increase in hemoglobin and improvement in fatigue without an increase in the overall frequency of adverse events.

The well-being of long-term cancer survivors.

OBJECTIVES: To compare the well-being of long-term cancer survivors with that of US residents of similar age and demographic characteristics, patients recently diagnosed with cancer, and individuals with chronic illness. STUDY DESIGN: Retrospective observational study. METHODS: Using the Health and Retirement Study, a survey of US residents older than 50 years, we defined 4 cohorts: long-term cancer survivors (>4 years post diagnosis), individuals recently diagnosed with cancer (≤4 years post diagnosis), individuals with chronic illness, and US residents older than 50 years ("nationally representative cohort"). Well-being measures included self-reported health, utility, happiness, medical utilization and spending, employment, and earnings, and these measures were compared across cohorts, adjusting for survey year, demographic characteristics, smoking, and number of comorbidities. We imputed medical spending using the Medical Expenditure Panel Survey and the Medicare Current Beneficiary Survey. RESULTS: Long-term cancer survivors fared significantly better than those recently diagnosed with cancer, those with chronic illness, and individuals in the nationally representative cohort in the majority of well-being measures (P <.05), including fewer doctor visits, hospitalizations, and hospital nights; better utility and self-reported health; and greater likelihood of employment. Long-term cancer survivors had lower healthcare spending than those recently diagnosed with cancer (P <.01) and significantly greater happiness than the nationally representative cohort and those with chronic illness (P <.05). CONCLUSIONS: Although patients with cancer experience diminished well-being in the short term across a variety of measures, in the long term, cancer survivors do as well as or better than US residents of similar age and demographic characteristics. This finding is striking given that one might expect long-term cancer survivors to do worse than similar individuals without a history of cancer.

Patient Versus Physician Valuation of Durable Survival Gains: Implications for Value Framework Assessments.

BACKGROUND: Previous research indicates that patients value therapies that provide durable or tail-of-the-curve survival gains, but it is unclear whether physicians share these preferences. OBJECTIVE: To compare patient and physician preferences for treatments with a positive probability of durable survival gains relative to those with fixed survival gains. METHODS: Patients with advanced stage melanoma or lung cancer and the oncologists who treated these patients were surveyed. The primary end point was the share of respondents who selected a therapy with a variable survival profile, with some patients experiencing long-term durable survival and others experiencing much shorter survival, compared to a therapy with a fixed survival duration. Parameter estimation by sequential testing was applied to calculate the length of nonvarying survival that would make respondents indifferent between that survival and therapy with durable survival. RESULTS: The sample comprised 165 patients (lung = 84, melanoma = 81) and 98 physicians. For lung cancer, 65.5% of patients preferred the therapy with a variable survival profile, compared with 40.8% of physicians (Δ = 24.7%; P < 0.001). For melanoma, these figures were 63.0% for patients and 29.7% for physicians (Δ = 33.3%; P < 0.001). Patients' indifference point implied that therapies with a variable survival profile are preferred unless the treatment with fixed survival had 13.6 months (melanoma) or 11.6 months (lung) longer mean survival; physicians would prescribe treatments with a fixed survival if the treatment had 7.5 months (melanoma) or 1.0 month (lung) shorter survival than the variable survival profile. CONCLUSIONS: Patients place a high value on therapies that provide a chance of durable or "tail-of-the-curve" survival, whereas physicians do not. Value frameworks should incorporate measures of tail-of-the-curve survival gains into their methodologies.

The Effectiveness of Tyrosine Kinase Inhibitors and Molecular Monitoring Patterns in Newly Diagnosed Patients With Chronic Myeloid Leukemia in the Community Setting.

BACKGROUND: Clinical outcomes of patients with chronic myeloid leukemia (CML) treated in clinical trials, including response to therapy, may not be representative of those treated in a community setting. Thus, we sought to determine the real-world effectiveness of first-line tyrosine kinase inhibitors in CML by evaluating response rates, all-cause discontinuation, and adherence. Response monitoring patterns were also analyzed. PATIENTS AND METHODS: This retrospective observational study, using the McKesson Specialty Health/US Oncology Network (MSH/USON) iKnowMed electronic health record database and medical charts, identified newly diagnosed CML patients who received first-line imatinib, dasatinib, or nilotinib from July 2007 to March 2011, and were then followed for ≥ 18 months. RESULTS: Three hundred patients met study criteria (222 imatinib-treated, 34 dasatinib-treated, and 44 nilotinib-treated in the first-line). Molecular and cytogenetic response assessments were conducted less frequently than recommended (40% never had cytogenetic or molecular monitoring at any time). Patients treated with either dasatinib or nilotinib experienced higher response rates by 6, 12, and 18 months, faster time to major molecular response, and a significantly lower rate of all-cause treatment discontinuation within 18 months relative to imatinib-treated patients. Approximately 56% of all patients were adherent to tyrosine kinase inhibitor therapy. CONCLUSION: Dasatinib and nilotinib were more effective than imatinib as first-line therapy for CML in a community setting, as observed in descriptive and univariate analyses. The frequency of cytogenetic and molecular monitoring was lower than that recommended by current guidelines, including patients with no molecular or cytogenetic assessments during the 18-month follow-up. Therefore, MSH/USON is working toward improving compliance with response monitoring guidelines.