Cost-Effectiveness Analysis of Pertuzumab With Trastuzumab and Chemotherapy Compared to Trastuzumab and Chemotherapy in the Adjuvant Treatment of HER2-Positive Breast Cancer in the United States.

OBJECTIVE: The APHINITY trial assessed the effectiveness and the safety of adding pertuzumab to trastuzumab and chemotherapy (THP) compared to trastuzumab and chemotherapy (TH) in the adjuvant management of human epidermal growth factor 2-positive (HER2+) breast cancer. We performed a study to project the potential cost-effectiveness of THP vs. TH. STUDY DESIGN: Trial-based cost-utility modeling analysis. METHODS: We performed an economic evaluation from a payer perspective using a Markov model with six health states: invasive disease-free survival, non-metastatic recurrence, remission, first-line metastatic, subsequent line metastatic, and death. We parameterized the model using data from both arms in APHINITY extrapolated to a patient's lifetime horizon. Estimates of health state utilities were based on EQ-5D trial data and the literature, and costs were estimated from government sources and the published literature. The primary outcomes of the model were life-years (LYs), quality-adjusted LYs (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Uncertainty was addressed via univariate and probabilistic sensitivity analyses. RESULTS: For the intention-to-treat population, the model projected improved outcomes (by 0.50 LYs and 0.45 QALYs) and increased costs (by $74 420) for ICERs of $147 774/LY gained and $167 185/QALY gained for PHT vs. HT patients. In the node-positive patient population, the model projected improved outcomes (by 0.86 LYs and 0.76 QALYs) and increased costs (by $66 647) for ICERs of $77 684/LY gained and $87 929/QALY gained. For the hormone-receptor-negative patient population, the model projected health gains, increased costs, and ICERs of $147 022/LY gained and $166 518/QALY gained. The results were sensitive to changes in the model time horizon. CONCLUSION: The addition of pertuzumab to the available regimens for HER2+ early breast cancer is likely to be cost-effective for patients in the U.S. at high risk of recurrence.

Most impactful factors on the health-related quality of life of a geriatric population with cancer.

BACKGROUND: As the population of older adults with cancer continues to grow, the most important factors contributing to their health-related quality of life (HRQOL) remain unclear. METHODS: A total of 1457 older adults (aged ≥65 years) with cancer participated in a telephone survey. Outcomes were measured using the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores of the 12-Item Short Form Survey (SF-12) from the Medical Outcomes Study (version 2). Statistical techniques used to identify factors in 4 domains (physical, psychological, social, and spiritual) most strongly associated with HRQOL included linear models, recursive partitioning, and random forests. Models were developed in a training data set (920 respondents) and performance was assessed in a validation data set (537 respondents). RESULTS: Respondents were a median of 19 months from diagnosis, and 28.1% were receiving active treatment. The most relevant factors found to be associated with PCS were symptom severity, comorbidity scores, leisure-time physical activity, and having physical support needs. The most relevant factors for MCS were having emotional support needs, symptom severity score, and the number of financial hardship events. Results were consistent across modeling techniques. Symptoms found to be strongly associated with PCS included fatigue (adjusted proportion of summary score's variance [R2 ] = 0.34), pain (adjusted R2 = 0.32), disturbed sleep (adjusted R2 = 0.16), and drowsiness (adjusted R2 = 0.16). Symptoms found to be strongly associated with MCS included fatigue (adjusted R2 = 0.23), problems remembering things (adjusted R2 = 0.17), disturbed sleep (adjusted R2 = 0.16), and lack of appetite (adjusted R2 = 0.16). CONCLUSIONS: The findings of the current study support the importance of addressing persistent symptoms, managing comorbidities, promoting leisure-time physical activity, and addressing financial challenges. A long-term comprehensive approach is needed to ensure the well-being of older adults with cancer. Cancer 2018;124:596-605. © 2017 American Cancer Society.

Impact of pharmacy channel on adherence to oral oncolytics.

BACKGROUND: Oral chemotherapy is increasingly prescribed to treat cancer. Despite its benefits, concerns have been raised regarding adherence to therapy. The study objective was to compare and measure adherence, persistence, and abandonment in patients filling prescriptions in traditional retail (TR) versus specialty pharmacy (SP) channels. METHODS: Using a retrospective cohort design, we selected newly treated patients aged ≥18 years with a prescription for erlotinib, capecitabine, or imatinib during 2007-2011 from a Medco population of both United States commercial and Medicare health plans. Patients were classified according to pharmacy channel providing the medication. Abandonment was defined as a reversal following initial approval of the index prescription claim with no additional paid claims for agent within 90 days of reversal. Patients were considered adherent if the proportion of days covered between the date of the first and last oral prescription was ≥80%. RESULTS: In our retrospective cohort, 11,972 filled their prescriptions within the SP channel, and 30,394 filled their prescriptions within the TR channels, respectively. The SP channel had the highest proportion of adherent patients compared with TR (71.6% vs. 56.4%, P < .001). Abandonment of the initial prescription was low with overall rates of only 1.7%. In multivariate models controlling for demographic characteristics, index oncolytic, days of supply, and copay, SP channel (relative to TR) was significantly associated with lower rates of abandonment and increased adherence. CONCLUSIONS: Pharmacy channel may be influential on abandonment and adherence. Lower rates of abandonment and higher rates of adherence were observed among SP patients versus TR.

Neoadjuvant Systemic Therapy for Breast Cancer: Factors Influencing Surgeons' Referrals.

BACKGROUND: This study aimed to assess the influence of disease- and patient-related factors on surgeons' decisions to refer patients with early-stage breast cancer (EBC) for neoadjuvant systemic therapy (NST). METHODS: An online survey of United States surgeons evaluated the influence of selected disease- and patient-related factors on surgeons' decisions, rated their influence (individually and in combination), and provided a relative ranking of jointly considered factors using best-worst scaling. RESULTS: The participants in this study were 100 licensed surgeons. The surgeons referred approximately 25 % of EBC patients for NST to improve surgical management. Approximately 75 % of the surgeons agreed that NST is important for EBC, if only to improve surgical management. More than half were "very likely" to refer EBC patients for NST based on anatomicopathologic factors. Less than 50 % were "very likely" to do so when considering tumor phenotype factors. Tumor size and lymph node status were ranked highest in hypothetical patient scenarios. Regarding combinations of factors, the importance of any single factor varied according to the combinations presented. Less than half of the respondents were "very familiar," and half were "somewhat familiar" with NST guidelines for breast cancer. More than half of the respondents were unaware that findings have shown achievement of pathologic complete response (pCR) after NST to be associated with improved survival. CONCLUSIONS: Surgeons' decision to refer for NST is strongly driven by surgical management goals. Anatomicopathologic factors are more influential than tumor phenotype. However, no single disease or patient factor consistently drives the decision to refer for NST. Surgeons' awareness of the association between pCR achievement and longer survival could be improved.

Survival and Racial Differences of Non-Small Cell Lung Cancer in the United States Military.

BACKGROUND: Lung cancer is the leading cause of cancer-related death in the United States (US) Military and worldwide, with non-small cell lung cancer (NSCLC) accounting for 87 % of cases. OBJECTIVES: Using a US military cohort who receives equal and open access to healthcare, we sought to examine demographic, clinical features and outcomes with NSCLC. DESIGN AND PARTICIPANTS: We conducted a retrospective cohort analysis of 4,751 patients, aged ≥ 18 years and diagnosed with a first primary NSCLC between 1 January 2003 and 31 December 2013 in the US Department of Defense (DoD) cancer registry. MAIN MEASURES: Differences by patient and disease characteristics were compared using Chi-square and t-test. Kaplan Meier curves and Cox proportional hazards regression assessed overall survival. RESULTS: The mean age at diagnosis was 66 years, 64 % were male, 72 % were Caucasian, 41 % were diagnosed at early stage, 77 % received treatment and 82 % had a history of tobacco use. Mean age at diagnosis was highest among Caucasians (67 years) and lowest among African Americans (AA; 62 years). Asian/Pacific Islanders (PI) were more likely to be female (p < 0.0001), have adenocarcinoma histology (p = 0.0003) and less likely to have a history of tobacco use (p < 0.0001) compared to other racial/ethnic groups. In multivariable survival analysis, older age, male gender, increasing stage, not receiving treatment, and tobacco history were associated with higher mortality risk. Untreated patients exhibited a 39 % higher mortality risk compared to treated patients (HR = 1.39; 95%CI = 1.23-1.57). Compared to Caucasian patients, Asian/PIs demonstrated a 20 % lower risk of death (HR = 0.80; 95%CI = 0.66-0.96). There was no difference in mortality risk between AAs and Hispanics compared to Caucasians. CONCLUSION: The lack of significant outcome disparity between AAs and Caucasians and the earlier stage at diagnosis than usually seen in civilian populations suggest that equal access to healthcare may play a role in early detection and survival.

Large-scale, prospective, observational studies in patients with psoriasis and psoriatic arthritis: A systematic and critical review.

BACKGROUND: Observational studies, if conducted appropriately, play an important role in the decision-making process providing invaluable information on effectiveness, patient-reported outcomes and costs in a real-world environment. We conducted a systematic review of large-scale, prospective, cohort studies with the aim of (a) summarising design characteristics, the interventions or aspects of the disease studied and the outcomes measured and (b) investigating methodological quality. METHODS: We included prospective, cohort studies which included at least 100 adults with psoriasis or psoriatic arthritis. Studies were identified through searches in electronic databases (Pubmed, Medline, Cochrane library, Centre for Reviews and Dissemination). Information on study characteristics were extracted and tabulated and quality assessment, using a checklist of 18 questions, was conducted. RESULTS: Thirty five papers covering 16 cohorts met the inclusion criteria. There were ten treatment-related studies, only two of which provided a comparison between treatments, and six non-treatment studies which examined a number of characteristics of the disease including mortality, morbidity, cost of illness and health-related quality of life. All studies included a clinical outcome measure and 11 included patient-reported outcomes, however only two studies reported information on patient utilities and two on costs. The quality of the assessed studies varied widely. Studies did well on a number of quality assessment questions including having clear objectives, documenting selection criteria, providing a representative sample, defining interventions/characteristics under study, defining and using appropriate outcomes, describing results clearly and using appropriate statistical tests. The quality assessment criteria least adhered to involved questions regarding sample size calculations, describing potential selection bias, defining and adjusting for confounders and losses to follow-up, and defining and describing a comparison group. CONCLUSION: The review highlights the need for well designed prospective observational studies on the effectiveness, patient-reported outcomes and economic impact of treatment regimes for patients with psoriasis and psoriatic arthritis in a real-world environment.

Understanding price growth in the market for targeted oncology therapies.

OBJECTIVES: The causes of oncology drug price growth remain unclear. Analyzing corresponding trends in revenue can help understand these causes. This study seeks to assess changes over time in prices, patient counts, and drug-level revenues in the US market for oncology therapies and to investigate whether price growth is driven by an increased ability by pharmaceutical firms to capture profits. STUDY DESIGN: Nineteen-year retrospective study (1997-2015). METHODS: We used panel regression to investigate trends in prices, patient counts, and revenues within a US national data set consisting of targeted oncology therapies launched in different eras. RESULTS: We find that prices have roughly tripled, whereas average patient counts per therapy have fallen by 85% to 90% over this period. However, the entire distribution of annual revenues has fallen: For instance, median revenues for drugs launched in the early 2010s are about half of what they were for drugs launched in the late 1990s. CONCLUSIONS: Future research on the causes of quantity decline can help inform pharmaceutical policy.

HER2-Positive Metastatic Breast Cancer Patients Receiving Pertuzumab in a Community Oncology Practice Setting: Treatment Patterns and Outcomes.

BACKGROUND: Pertuzumab (Perjeta®), a HER2/neu receptor antagonist, was approved by the US Food and Drug Administration in June 2012 for use in the first-line setting for patients with HER2-positive metastatic breast cancer (mBC). OBJECTIVE: This retrospective study investigated the clinical and demographic characteristics, treatment patterns, safety, and clinical outcomes for patients with HER2-positive mBC who received pertuzumab in the first-line setting in US community oncology practices. METHODS: Patients with HER2-positive mBC, who initiated pertuzumab within 60 days of mBC diagnosis between June 2012 and June 2014, followed through December 2014, had ≥2 visits within the McKesson Specialty Health/US Oncology Network, and were not on clinical trials during the study period, were eligible. This study utilized iKnowMed electronic health records, Claims Data Warehouse, and Social Security Death Index. Progression-free survival (PFS) was assessed by Kaplan-Meier methods. RESULTS: A total of 266 patients met the selection criteria. A vast majority of the patients (249/266, 93.6%) received a trastuzumab + pertuzumab + taxane (H + P + T) regimen. The number of patients with prior adjuvant/neoadjuvant therapy was higher than the CLEOPATRA trial, but age (median 57 years) and percentage of visceral disease (74.8%) were similar. The most common adverse events were fatigue (50.8%), diarrhea (44.7%), nausea (35.3%), peripheral neuropathy (33.5%), neutropenia (24.9%), and rash (24.4%). The median PFS was 16.9 months (95% CI 14.2-19.7). CONCLUSIONS: In this retrospective study of patients with HER2-positive mBC receiving pertuzumab in the first-line setting, most patients were treated with H + P + T. The safety and PFS of H + P + T were consistent with those observed in the pivotal trial.

First-Line Treatment with Bevacizumab and Platinum Doublet Combination in Non-Squamous Non-Small Cell Lung Cancer: A Retrospective Cohort Study in US Oncology Community Practices.

BACKGROUND: Real-world evidence is lacking on the impact of bevacizumab added to carboplatin/paclitaxel (Bev + CP) therapy versus CP alone for patients with non-squamous non-small cell lung cancer (NS-NSCLC), particularly in those excluded from clinical trials. METHODS: This is a retrospective electronic medical record analysis of patients who received first-line therapy with Bev + CP or CP between 1 October 2006 and 30 June 2013. We identified four subsets: elderly patients (≥65 years), patients with brain/central nervous system (CNS) metastases, patients with Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, and patients receiving anticoagulation. We used descriptive statistics to describe patient characteristics and treatment patterns and evaluated progression-free survival (PFS) and overall survival (OS) using survival analyses. RESULTS: The study included 431 patients (Bev + CP: 231; CP: 200). The Bev + CP cohort was more likely to receive four or more cycles of induction therapy (72 vs. 50 %) and was more likely to receive maintenance therapy (45 vs. 21 %) than patients receiving CP. In the overall population, median PFS and OS were significantly longer in the Bev + CP cohort than in the CP cohort: 6.7 vs. 5.1 months (hazard ratio [HR] 0.74; 95 % confidence interval [CI] 0.59-0.92; p = 0.008) and 11.9 vs. 9.0 months (HR 0.57; 95 % CI 0.44-0.73; p < 0.001), respectively. Treatment with Bev + CP in patients aged ≥65 years and in those with brain/CNS metastases was also associated with a significant risk reduction in PFS (35 and 51 %, respectively; p < 0.05 for both) and OS (46 and 62 %, respectively; p < 0.05 for both) compared with CP alone. CONCLUSION: Bev + CP is associated with a significant improvement in PFS and OS in patients with NS-NSCLC and in subsets with brain/CNS metastases and those aged ≥65 years.

Long-term treatment of atopic dermatitis with pimecrolimus cream 1% in infants does not interfere with the development of protective antibodies after vaccination.

OBJECTIVE: We investigated whether treatment of atopic dermatitis with pimecrolimus cream 1% in infants affects the development of a normal antibody response to vaccinations. METHODS: In all, 91 patients participated in a 1-year, open-label extension to a 1-year double-blind study: 76 used pimecrolimus twice daily at the first signs or symptoms of the disease until clearance for 2 years and 15 only in the second year. Serum concentrations of antibodies against tetanus, diphtheria, measles, and rubella were measured at months 18 and 24. RESULTS: The seropositivity rates of 93.6% for tetanus, 88.6% for diphtheria, 88.5% for measles, and 84.4% for rubella were comparable with those reported in literature. Seropositivity was not significantly affected by the use of pimecrolimus at the time of vaccinations (+/- 28 days). CONCLUSIONS: Treatment of atopic dermatitis with pimecrolimus cream 1% in early childhood does not appear to interfere with the development of a normal immune response to vaccinations.

Long-term control of atopic dermatitis with pimecrolimus cream 1% in infants and young children: a two-year study.

OBJECTIVE AND METHODS: The safety and efficacy of treatment with pimecrolimus cream 1% was evaluated for up to 2 years in infants and young children with atopic dermatitis. Ninety-one patients participated in a 1-year, open-label extension to a 1-year double-blind study. Of these, 76 received pimecrolimus for 2 years. Pimecrolimus was applied twice daily at the first signs or symptoms of the disease until clearance. Outcome measures included the incidence of adverse events and the Eczema Area and Severity Index (EASI). RESULTS: No patient discontinued because of adverse events. The incidence of systemic and skin infections did not increase over time. Over the 2-year period, 2 patients experienced an episode of clinically diagnosed eczema herpeticum. In patients receiving pimecrolimus for 2 years, the mean decrease in EASI score from baseline was 68.7% at 3 months and 70.8% at 24 months. CONCLUSION: Treatment with pimecrolimus cream 1% for up to 2 years was well tolerated and resulted in a marked and sustained improvement of atopic dermatitis.

Targeted erlotinib for first-line treatment of advanced non-small cell lung cancer: a budget impact analysis.

OBJECTIVES: A recent phase III trial showed that patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor specific EGFR mutations significantly benefit from first-line treatment with erlotinib compared to chemotherapy. This study sought to estimate the budget impact if coverage for EGFR testing and erlotinib as first-line therapy were provided in a hypothetical 500,000-member managed care plan. METHODS: The budget impact model was developed from a US health plan perspective to evaluate administration of the EGFR test and treatment with erlotinib for EGFR-positive patients, compared to non-targeted treatment with chemotherapy. The eligible patient population was estimated from age-stratified SEER incidence data. Clinical data were derived from key randomized controlled trials. Costs related to drug, administration, and adverse events were included. Sensitivity analyses were conducted to assess uncertainty. RESULTS: In a plan of 500,000 members, it was estimated there would be 91 newly diagnosed advanced NSCLC patients annually; 11 are expected to be EGFR-positive. Based on the testing and treatment assumptions, it was estimated that 3 patients in Scenario 1 and 6 patients in Scenario 2 receive erlotinib. Overall health plan expenditures would increase by $0.013 per member per month (PMPM). This increase is largely attributable to erlotinib drug costs, in part due to lengthened progression-free survival and treatment periods experienced in erlotinib-treated patients. EGFR testing contributes slightly, whereas adverse event costs mitigate the budget impact. The budget impact did not exceed $0.019 PMPM in sensitivity analyses. CONCLUSIONS: Coverage for targeted first-line erlotinib therapy in NSCLC likely results in a small budget impact for US health plans. The estimated impact may vary by plan, or if second-line or maintenance therapy, dose changes/interruptions, or impact on patients' quality-of-life were included.