Cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy for treating previously treated advanced endometrial cancer in Sweden.

OBJECTIVE: Pembrolizumab plus lenvatinib was recently approved for the treatment of advanced or recurrent endometrial carcinoma in women with disease progression on or following prior treatment with a platinum­containing therapy in any setting, and who are not candidates for curative surgery or radiation (KEYNOTE-775/Study-309; NCT03517449). The objective was to assess the cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy from a Swedish healthcare perspective. MATERIALS AND METHODS: A lifetime partitioned-survival model with three health states (progression free, progressed disease, death) was constructed. Chemotherapy was represented by paclitaxel or doxorubicin. Overall survival, progression-free survival, time on treatment, and utility data were obtained from KEYNOTE-775 (database lock: March 1, 2022). Costs (in 2020 Swedish Krona [SEK]) included drug acquisition and administration, health state, end of life, adverse event management, subsequent treatment, and societal (scenario analysis). Outcomes were calculated as quality-adjusted life-years (QALY) and life-years. Model results were presented as incremental cost-effectiveness ratios for all-comers, patients with proficient mismatch repair tumors, and deficient mismatch repair tumors. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Pembrolizumab plus lenvatinib is a cost-effective treatment when compared with chemotherapy, with estimated deterministic and probabilistic incremental cost-effectiveness ratios of SEK 795,712 and 819,757 per QALY gained. Pembrolizumab plus lenvatinib was associated with a large incremental QALY and life-year gain per person versus chemotherapy over the model time horizon (1.49 and 1.76). LIMITATIONS: Time-to-event data were incomplete and semiparametric and parametric curves were utilized for lifetime extrapolation. Willingness-to-pay thresholds, costs, and utility weights vary by country, which would vary the treatment's cost effectiveness in different countries. CONCLUSIONS: This partitioned survival analysis suggests that pembrolizumab plus lenvatinib is cost effective compared with chemotherapy in Sweden for women with advanced or recurrent endometrial carcinoma following previous systemic therapy. Results were robust to mismatch repair status and to changes in parameters/assumptions.

Impact of geographic access to primary care providers on pediatric behavioral health screening.

Behavioral Health (BH) screening is critical for early diagnosis and treatment of pediatric mental disorders. The objective of this study was to assess the impact of geographic access to primary care providers (PCP) on pediatric BH screening in children with different race/ethnicity. A retrospective cohort study was conducted using the 2013-2016 administrative claims data from a large pediatric Medicaid Managed Care Plan that have been linked to 2010 US Census data and the 2017 National Provider Identifier (NPI) Registry. Geographic access was defined as the actual travel distance to nearest PCP and the PCP density within 10-mile travel radius from each individual's residence. Stratified multivariate logistic regression was conducted to examine the association between the geographic access to PCP and the likelihood of receiving screening for behavioral disorders within each racial/ethnic group. BH screening rate was 12.6% among 402,655 children and adolescents who met the inclusion criteria. Multivariable analysis stratified by individual race/ethnicity revealed that Hispanic and Black children were more vulnerable to the geographic access barriers than their non-Hispanic White counterparts. The increase in travel distance to the nearest PCP was negatively associated with screening uptake only among Hispanics (10-20 miles vs. 0-10 miles: OR = 0.78, 95% CI [0.71-0.86]; 20-30 miles vs. 0-10 miles: OR = 0.35, 95% CI [0.23-0.54]). In a subgroup that had access to at least one PCP within 10 miles of travel distance, the variation in PCP density had a greater impact on the screening uptake among Hispanics and Blacks than that in non-Hispanic Whites.

Cost-effectiveness of pembrolizumab compared with chemotherapy in the US for women with previously treated deficient mismatch repair or high microsatellite instability unresectable or metastatic endometrial cancer.

AIMS: There is limited published evidence for the cost-effectiveness of treatments for unresectable or metastatic endometrial cancer (mEC). The objective of this analysis was to assess the cost-effectiveness of pembrolizumab versus chemotherapy for previously treated unresectable or mEC, in women whose tumors have deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H). The analysis was carried out from a US healthcare payer perspective. MATERIALS AND METHODS: A lifetime partitioned survival model comprising three health states (progression-free, progressed disease and death) was constructed. Chemotherapy was represented by single-agent paclitaxel or doxorubicin. Overall survival, progression-free survival and time on treatment data for pembrolizumab were obtained from a Phase II clinical study that included women with previously treated dMMR/MSI-H unresectable or mEC (KEYNOTE-158, NCT02628067). Survival data for chemotherapy were obtained from a published Phase III study for previously treated advanced endometrial cancer. Costs included were drug acquisition and administration, health-state, end-of-life, and adverse event management. Costs were presented in 2019 US$. Outcomes were calculated as quality-adjusted life-years (QALYs), using EQ-5D data from KEYNOTE-158. Model results were tested extensively in deterministic and probabilistic sensitivity analyses. RESULTS: Results demonstrated that pembrolizumab is a highly cost-effective treatment option when compared with chemotherapy, with estimated deterministic and probabilistic incremental cost-effectiveness ratios (ICERs) of $58,165 and $57,668 per QALY gained, respectively. Pembrolizumab was associated with a large QALY and life-year gain per person versus chemotherapy over the model time horizon (deterministic 4.68 life year gain, 3.80 QALYs), with the majority of QALYs accrued in the progression-free health state. LIMITATIONS: The key limitation of the analysis was the lack of comparative effectiveness data for pembrolizumab versus chemotherapy. CONCLUSIONS: Pembrolizumab is a highly cost-effective treatment option when compared with chemotherapy for women with previously treated dMMR/MSI-H unresectable or mEC. Results were robust to the changes in parameters and assumptions explored.

Quetiapine Fumarate Loaded Nanostructured Lipid Carrier for Enhancing Oral Bioavailability: Design, Development and Pharmacokinetic Assessment.

AIMS: The study aimed at developing and characterizing Nanostructured Lipid Carriers (NLC) of Quetiapine Fumarate (QF) by Design of Experiment (DoE) for the enhancement of bioavailability. BACKGROUND: QF, an anti-psychotic drug, has an oral bioavailability of 9% due to hepatic first- pass metabolism necessitating the use of high doses. Its side effects are dose -related and enhancement in bioavailability would result in minimization of side effects. OBJECTIVE: The objective of the study was the enhancement of bioavailability of the NLC of QF by preferential lymphatic uptake. METHODS: Hot emulsification-ultrasonication was the method of formulation using PrecirolATO5 and Oleic acid as solid and liquid lipids respectively. Poloxamer188 and Phospholipon90G were used as surfactant and stabilizer respectively. Solid:liquid lipid ratio and Phospholipon90G amount were independent variables and percent Entrapment Efficiency (%EE), Particle Size (PS) dependent variables during optimization by Central Composite Design. RESULTS: The optimized formulation showed a %EE of 77.21%, PS of 140.2 nm and surface charge of - 19.9mV. Higuchi kinetic model was followed during the in-vitro release. TEM revealed spherical, smooth nanoparticles. A pharmacokinetic study in rats showed AUC0-∞ of QF-NLC to be 3.93 times that of QF in suspension, suggesting significant enhancement in bioavailability. An increase in AUC0-∞ in cycloheximide untreated rats' group of QF-NLC by 2.43 times as compared to cycloheximide treated group, confirmed lymphatic absorption of QF- NLC. CONCLUSION: The results validated DoE as an appropriate tool for developing QF loaded NLC and proved NLC to be a promising delivery system for the enhancement of oral bioavailability of QF.

The association between geographic access to providers and the treatment quality of pediatric depression.

OBJECTIVE: To examine the association of geographic access to providers with racial/ethnic variations in treatment quality among youth with depression. METHODS: The geographic access to providers who initiated the depression treatment was measured using the travel distance estimated based on Google Maps® and the provider density within a 5-mile radius of each patient residence. Depression treatment quality was measured as treatment engagement, defined as having ≥2 prescriptions or psychotherapy with 2-month following a new depression diagnosis, and treatment completion defined as having ≥8 sessions of psychotherapy within 12 weeks or received ≥84 days of continuous treatment with antidepressants within 114 days following the treatment initiation. RESULTS: The results of multivariate logistic regression analysis have demonstrated that the travel distance to provider was only negatively associated with the treatment engagement of Hispanics (5.0 - 14.9 vs ≤ 4.9 miles: OR=0.74, 95% CI [0.54-0.88]; ≥15 vs ≤ 4.9 miles: OR=0.82, 95% CI [0.56-0.97]), while a higher mental health specialist density was only positively associated with the treatment engagement of Blacks (1.00-1.99 vs < 1.00: OR=1.63, 95% CI [1.03-4.51]; 2.00-4.99 vs < 1.0: OR=2.28, 95% CI [1.21-7.11]). Among those who have engaged in the treatment, travel distance was associated with a lower likelihood of treatment completion in all racial/ethnic groups. LIMITATIONS: The study did not account for types of transportation used by patients. CONCLUSION: Geographic access barriers had a negative association with treatment quality of pediatric depression. Minority children were more sensitive to the barriers than Whites.