BackgroundRapidly evolving understanding of cancer biology has presented novel opportunities to translate that understanding into clinically relevant therapy. Palbociclib, a novel, first-in-class cyclin-dependent kinase (CDK) 4/6 inhibitor was approved in the USA in February 2015 for the treatment of advanced/metastatic breast cancer. We examined real-world evidence in the first year post approval to understand the clinical and demographic characteristics of patients treated with palbociclib in community oncology practices and the dosing, treatment, and complete blood count (CBC) monitoring patterns.MethodsThis was a retrospective observational study of structured data from a US electronic medical record (EMR) database. Female patients receiving palbociclib after 31 January 2015 were followed through 31 March 2016. Our methodological rules were constructed to aggregate drugs received according to the order in which they are given, i.e., identify the line of therapy as first, second, or third line, etc., using treatment order and course description fields from the EMR.ResultsThere were 763 patients initiating palbociclib who met the selection criteria. Of those, 612 (80.2%) received palbociclib concomitantly with letrozole. Mean follow up was 6.4 months and mean age at palbociclib initiation was 64 years. Of patients with a known starting dose (n = 417), 79.9% started on palbociclib 125 mg. Dose reductions were observed in 20.1% of patients. Percentages of patients according to line of therapy at initiation of palbociclib were first-line, 39.5%; second-line, 15.7%; third-line, 13.1%; and fourth-line therapy or later, 31.7%. On average, two CBC tests were conducted during the first cycle of palbociclib treatment. Overall, 74.6% of patients had a neutropenic event during follow up including 47.3% and 8.0% of patients with a grade 3 or 4 occurrence, respectively.ConclusionsReal-world palbociclib use one year post US approval demonstrates a more heterogeneous patient population than that studied in the clinical trials with more than half of the patients receiving palbociclib plus letrozole in later lines of therapy. CBC testing rates suggested good provider compliance with monitoring guidelines in the USA prescribing information. The occurrence of grade 3 and 4 neutropenia (based on laboratory results) was consistent with the rates of grade 3 and 4 neutropenia in two phase-III studies (PALOMA-2, 56% and 10%; PALOMA-3, 55% and 11%, respectively). Understanding palbociclib utilization in real-world patients and how drug dosing and monitoring are performed aids in the understanding of safe and effective use of the drug.Electronic supplementary materialThe online version of this article (10.1186/s13058-018-0958-2) contains supplementary material, which is available to authorized users.
BackgroundThirteen-valent pneumococcal conjugate vaccine (PCV13) and 10-valent pneumococcal conjugate vaccine (PCV10) are two recently approved vaccines for the active immunization against Streptococcus pneumoniae causing invasive pneumococcal disease in infants and children. PCV13 offers broader protection against Streptococcus pneumoniae; however, PCV10 offers potential protection against non-typeable Haemophilus influenza (NTHi). We examined public health and economic impacts of a PCV10 and PCV13 pediatric national immunization programs (NIPs) in Canada.MethodsA decision-analytic model was developed to examine the costs and outcomes associated with PCV10 and PCV13 pediatric NIPs. The model followed individuals over the remainder of their lifetime. Recent disease incidence, serotype coverage, population data, percent vaccinated, costs, and utilities were obtained from the published literature. Direct and indirect effects were derived from 7-valent pneumococcal vaccine. Additional direct effect of 4% was attributed to PCV10 for moderate to severe acute otitis media to account for potential NTHi benefit. Annual number of disease cases and costs (2010 Canadian dollars) were presented.ResultsIn Canada, PCV13 was estimated to prevent more cases of disease (49,340 when considering both direct and indirect effects and 7,466 when considering direct effects only) than PCV10. This translated to population gains of 258 to 13,828 more quality-adjusted life-years when vaccinating with PCV13 versus PCV10. Annual direct medical costs (including the cost of vaccination) were estimated to be reduced by $5.7 million to $132.8 million when vaccinating with PCV13. Thus, PCV13 dominated PCV10, and sensitivity analyses showed PCV13 to always be dominant or cost-effective versus PCV10.ConclusionsConsidering the epidemiology of pneumococcal disease in Canada, PCV13 is shown to be a cost-saving immunization program because it provides substantial public health and economic benefits relative to PCV10.
Background. Routine vaccination against Streptococcus pneumoniae is recommended in Canada for infants, the elderly, and individuals with chronic comorbidity. National incidence and burden of all-cause and pneumococcal pneumonia in Canada (excluding Quebec) were assessed. Methods. Incidence, length of stay, and case-fatality rates of hospitalized all-cause and pneumococcal pneumonia were determined for 2004–2010 using ICD-10 discharge data from the Canadian Institutes for Health Information Discharge Abstract Database. Population-at-risk data were obtained from the Statistics Canada census. Temporal changes in pneumococcal and all-cause pneumonia rates in adults ≥65 years were analyzed by logistic regression. Results. Hospitalization for all-cause pneumonia was highest in children <5 years and in adults >70 years and declined significantly from 1766/100,000 to 1537/100,000 per year in individuals aged ≥65 years (P < 0.001). Overall hospitalization for pneumococcal pneumonia also declined from 6.40/100,000 to 5.08/100,000 per year. Case-fatality rates were stable (11.6% to 12.3%). Elderly individuals had longer length of stay and higher case-fatality rates than younger groups. Conclusions. All-cause and pneumococcal pneumonia hospitalization rates declined between 2004 and 2010 in Canada (excluding Quebec). Direct and indirect effects from pediatric pneumococcal immunization may partly explain some of this decline. Nevertheless, the burden of disease from pneumonia remains high.
BackgroundAdjuvant sunitinib has significantly improved disease-free survival versus placebo in patients with renal cell carcinoma at high risk of recurrence post-nephrectomy (hazard ratio 0.76; 95% confidence interval, 0.59–0.98; two-sided P = 0.03). We report safety, therapy management, and patient-reported outcomes for patients receiving sunitinib and placebo in the S-TRAC trial.Patients and methodsPatients were stratified by the University of California, Los Angeles Integrated Staging System and Eastern Cooperative Oncology Group performance status score, and randomized (1 : 1) to receive sunitinib (50 mg/day) or placebo. Single dose reductions to 37.5 mg, dose delays, and dose interruptions were used to manage adverse events (AEs). Patients’ health-related quality of life, including key symptoms typically associated with sunitinib, were evaluated with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).ResultsPatients maintained treatment for 9.5 (mean, SD 4.4) and 10.3 (mean, SD 3.7) months in the sunitinib and placebo arms, respectively. In the sunitinib arm, key AEs occurred ∼1 month (median) after start of treatment and resolved within ∼3.5 weeks (median). Many (40.6%) AEs leading to permanent discontinuation were grade 1/2, and most (87.2%) resolved or were resolving by 28 days after last treatment. Patients taking sunitinib showed a significantly lower EORTC QLQ-C30 overall health status score versus placebo, although this reduction was not clinically meaningful. Patients reported symptoms typically related to sunitinib treatment with diarrhea and loss of appetite showing clinically meaningful increases.ConclusionsIn S-TRAC, AEs were predictable, manageable, and reversible via dose interruptions, dose reductions, and/or standard supportive medical therapy. Patients on sunitinib did report increased symptoms and reduced HRQoL, but these changes were generally not clinically meaningful, apart from appetite loss and diarrhea, and were expected in the context of known sunitinib effects.Clinical trial registrationClinicalTrials.gov, NCT00375674.
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