Challenges with Estimating Long-Term Overall Survival in Extensive Stage Small-Cell Lung Cancer: A Validation-Based Case Study.

Objective: The study aimed to explore methods and highlight the challenges of extrapolating the overall survival (OS) of immunotherapy-based treatment in first-line extensive stage small-cell lung cancer (ES-SCLC). Methods: Standard parametric survival models, spline models, landmark models, mixture and non-mixture cure models, and Markov models were fitted to 2-year data of the CASPIAN Phase 3 randomised trial of PD-L1 inhibitor durvalumab added to platinum-based chemotherapy (NCT03043872). Extrapolations were compared with updated 3-year data from the same trial and the plausibility of long-term estimates assessed. Results: All models used provided a reasonable fit to the observed Kaplan-Meier (K-M) survival data. The model which provided the best fit to the updated CASPIAN data was the mixture cure model. In contrast, the landmark analysis provided the least accurate fit to model survival. Estimated mean OS differed substantially across models and ranged from (in years) 1.41 (landmark model) to 4.81 (mixture cure model) for durvalumab plus etoposide and platinum and from 1.01 (landmark model) to 2.00 (mixture cure model) for etoposide and platinum. Conclusion: While most models may provide a good fit to K-M data, it is crucial to assess beyond the statistical goodness-of-fit and consider the clinical plausibility of the long-term predictions. The more complex cure models demonstrated the best predictive ability at 3 years, potentially providing a better representation of the underlying method of action of immunotherapy; however, consideration of the models' clinical plausibility and cure assumptions need further research and validation. Our findings underscore the significance of adopting a clinical perspective when selecting the most appropriate approach to model long-term survival, particularly when considering the use of more complex models.

Cost-effectiveness of acalabrutinib regimens in treatment-naïve chronic lymphocytic leukemia in the United States.

BACKGROUND: Clinical outcomes in chronic lymphocytic leukemia (CLL) have improved with targeted therapy, including Bruton tyrosine kinase inhibitors such as acalabrutinib. METHODS: A semi-Markov model with three health states (progression-free, progressed disease, and death) estimated cost per quality-adjusted life-year (QALY) gained for acalabrutinib ± obinutuzumab vs chlorambucil + obinutuzumab in treatment-naive CLL (based on ELEVATE-TN). The model used direct costs and resource utilization from the US Medicare perspective and utility values sourced from literature. Sensitivity analyses tested the robustness of the model. RESULTS: Over a 30-year lifetime horizon, the model base case analysis suggested that acalabrutinib monotherapy had an incremental cost of $206,329 and 2.52 QALYs gained versus chlorambucil + obinutuzumab, resulting in an incremental cost-effectiveness ratio (ICER) of $81,960/QALY. Acalabrutinib + obinutuzumab had an incremental cost of $423,747 and 2.79 QALYs gained (ICER: $152,153/QALY). Probabilistic sensitivity analysis showed the probability of acalabrutinib monotherapy being cost-effective as 59% to 73% at a $100,000-to-150,000/QALY willingness-to-pay threshold; the probability of acalabrutinib + obinutuzumab being cost-effective ranged from 34% to 51%. CONCLUSIONS: Although the analysis is limited by uncertainty in postprogression survival outcomes, acalabrutinib monotherapy is likely cost-effective vs chlorambucil + obinutuzumab in treatment-naive CLL in the US Medicare setting.

Greater prevalence of comorbidities with increasing age: Cross-sectional analysis of chronic hepatitis B patients in Saudi Arabia.

BACKGROUND/AIMS: Middle Eastern countries, including Saudi Arabia to some extent, are endemic for chronic hepatitis B (CHB) infection which could be associated with high mortality and comorbidities risk. However, limited data characterizing this CHB population exists. Our aim was to characterize and compare CHB patients in 2015 with those in 2010 and 2012 in Saudi Arabia. PATIENTS AND METHODS: We conducted and compared three cross-sectional analyses of adult patients with CHB defined as either positive hepatitis B surface antigen or documented CHB history in 2010, 2012, and 2015. Data were accessed from the multicenter Systematic Observatory Liver Disease Registry (SOLID). RESULTS: A total of 765 CHB patients were identified in 2010 (n = 274), 2012 (n = 256), and 2015 (n = 235). Median age was significantly higher in 2015 (47 years) compared to 2010 and 2012 (42 years;P < 0.05). The proportions of patients with hepatocellular carcinoma (range 1-12%) and cirrhosis (range 5-23%) were significantly higher in 2015 compared to 2010 and 2012 (P < 0.05). Compared to 2010, patients in 2015 had significantly (P < 0.05) higher prevalence of coronary artery disease (10% vs. 4%) and hyperbilirubinemia (18% vs. 9%). Although not significant, there was a numerical increase in 2015 in chronic kidney disease (9% vs. 7% in 2010;P= 0.559) and hepatic steatosis (32% vs. 25% in 2010;P= 0.074). Significantly more patients in 2015 (P < 0.05) were treatment experienced (23% vs. 5% in 2010/2012) and switched treatment (17% vs. 1-2% in 2010/2012). CONCLUSIONS: Between 2010 and 2015, the CHB population in Saudi Arabia had significantly aged and was more likely to develop liver disease sequelae and other comorbidities.