Johanna Lister

Cost‐effectiveness of bevacizumab‐based therapy versus cisplatin plus pemetrexed for the first‐line treatment of advanced non‐squamous NSCLC in Korea and Taiwan

Aims:  The aim of this analysis is to investigate the mean incremental costs and life expectancy associated with two first‐line treatments for advanced non‐squamous non‐small cell lung cancer (NSCLC) in Korea and Taiwan; bevacizumab plus cisplatin and gemcitabine (BevCG) and cisplatin plus pemetrexed (CP).

Clinical and cost effectiveness of bevacizumab + FOLFIRI combination versus FOLFIRI alone as first-line treatment of metastatic colorectal cancer in South Korea.

BACKGROUND Bevacizumab has been extensively investigated in combination with various standard chemotherapies in the treatment of metastatic colorectal cancer (mCRC). However, a comparison to irinotecan + infusional 5-fluorouracil/leucovorin (FOLFIRI) is lacking. OBJECTIVE To explore clinical effectiveness and cost-effectiveness of adding bevacizumab to a regimen of FOLFIRI for the first-line treatment of mCRC in the Republic of Korea by conducting an indirect treatment comparison. METHODS A health-economic model was developed to investigate the possible health outcomes (life-years gained [LYG]), direct costs, and incremental cost-effectiveness ratio (ICER) of adding bevacizumab to a FOLFIRI regimen. Data on progression-free and overall survival were derived from randomized clinical trials and were used in the indirect treatment comparison. The annual discount rate for costs and outcomes was 5%. A lifetime horizon of 8 years was used. Sensitivity analyses were carried out on all pivotal model assumptions. RESULTS Incremental mean overall survival among patients treated with bevacizumab + FOLFIRI varied between 8.6 and 15.7 months compared with patients treated with FOLFIRI alone. The deterministic base-case result was 1.177 LYG. The discounted ICERs ranged from μ31.8 to μ39.5 million/LYG, with the base-case result being μ34.5 million/LYG. Treatment effect had the most impact on the outcomes in this model. CONCLUSIONS Although there is no formal threshold for ICER per LYG in Korea, funding may be considered for bevacizumab + FOLFIRI, particularly if the severity and end-of-life nature of mCRC is taken into account.

Cabozantinib versus everolimus, nivolumab, axitinib, sorafenib and best supportive care: A network meta-analysis of progression-free survival and overall survival in second line treatment of advanced renal cell carcinoma

Background Relative effect of therapies indicated for the treatment of advanced renal cell carcinoma (aRCC) after failure of first line treatment is currently not known. The objective of the present study is to evaluate progression-free survival (PFS) and overall survival (OS) of cabozantinib compared to everolimus, nivolumab, axitinib, sorafenib, and best supportive care (BSC) in aRCC patients who progressed after previous VEGFR tyrosine-kinase inhibitor (TKI) treatment. Methodology & findings Systematic literature search identified 5 studies for inclusion in this analysis. The assessment of the proportional hazard (PH) assumption between the survival curves for different treatment arms in the identified studies showed that survival curves in two of the studies did not fulfil the PH assumption, making comparisons of constant hazard ratios (HRs) inappropriate. Consequently, a parametric survival network meta-analysis model was implemented with five families of functions being jointly fitted in a Bayesian framework to PFS, then OS, data on all treatments. The comparison relied on data digitized from the Kaplan-Meier curves of published studies, except for cabozantinib and its comparator everolimus where patient level data were available. This analysis applied a Bayesian fixed-effects network meta-analysis model to compare PFS and OS of cabozantinib versus its comparators. The log-normal fixed-effects model displayed the best fit of data for both PFS and OS, and showed that patients on cabozantinib had a higher probability of longer PFS and OS than patients exposed to comparators. The survival advantage of cabozantinib increased over time for OS. For PFS the survival advantage reached its maximum at the end of the first year’s treatment and then decreased over time to zero. Conclusion With all five families of distributions, cabozantinib was superior to all its comparators with a higher probability of longer PFS and OS during the analyzed 3 years, except with the Gompertz model, where nivolumab was preferred after 24 months.

Cabozantinib Versus Standard-of-Care Comparators in the Treatment of Advanced/Metastatic Renal Cell Carcinoma in Treatment-naïve Patients: a Systematic Review and Network Meta-Analysis

BackgroundCabozantinib has recently been evaluated as a first-line treatment in advanced renal cell carcinoma (aRCC).ObjectiveTo indirectly assess efficacy of cabozantinib versus standard-of-care (SoC) comparators in the first-line treatment of aRCC.MethodsWe conducted a systematic literature review (SLR) to identify randomized controlled studies in the first-line setting for aRCC. The outcomes analyzed were overall survival (OS) and progression-free survival (PFS). A network meta-analysis (NMA) was conducted comparing OS and PFS hazard ratios (HRs).ResultsThirteen studies were identified in the SLR to be eligible for inclusion in the NMA. The overall study populations were heterogeneous in terms of risk groups; some studies included favorable risk patients. In intermediate-risk patients, HRs (95% confidence interval) for PFS were 0.52 (0.33, 0.82), 0.46 (0.26, 0.80), 0.20 (0.12, 0.36), and 0.37 (0.20, 0.68) when cabozantinib was compared with sunitinib, sorafenib, interferon (IFN), or bevacizumab plus IFN, respectively. In poor-risk patients, the NMA also demonstrated significant superiority in terms of PFS for cabozantinib; HRs were 0.31 (0.11, 0.90), 0.22 (0.06, 0.87), 0.16 (0.04, 0.64), and 0.20 (0.05, 0.88), when cabozantinib was compared with sunitinib, temsirolimus, IFN, or bevacizumab plus IFN, respectively. When the overall study populations were compared, the results were similar to the subgroup analyses. OS HRs in all analyses favored cabozantinib, but were not statistically significant.ConclusionsThe results suggest that cabozantinib significantly increases PFS in intermediate-, and poor-risk subgroups when compared to standard-of-care comparators. Although overall populations included favorable risk patients in some studies, the results seen were consistent with the subgroup analyses.

Simulation and comparison of progression-free survival among patients with non-squamous non-small-cell lung cancer receiving sequential therapy.

Objectives: In recent years, the treatment landscape in advanced non-squamous non-small-cell lung cancer (nsNSCLC) has changed. New therapies (e.g., bevacizumab indicated in first line) have become available and other therapies (e.g., pemetrexed in first line and second line) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is still a key research question which therapy sequence results in the best survival outcomes for patients with nsNSCLC. Methods: A therapy-sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for progression-free survival (PFS) and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, received first-line treatment with either bevacizumab-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin). Patients would then progress to a subsequent line of therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy, based on EMA licensed therapies. Weibull distribution curves were fitted to the data. Results: All bevacizumab-based first-line therapy sequences analyzed achieved total PFS of around 15 months. Bevacizumab + carboplatin + paclitaxel (first line) → pemetrexed (second line) → erlotinib (third line) → docetaxel (fourth line) resulted in total mean PFS time of 15.7 months, for instance. Sequences with pemetrexed in combination with cisplatin in first line achieved total PFS times between 12.6 and 12.8 months with a slightly higher total PFS time achieved when assuming pemetrexed continuation therapy in maintenance after pemetrexed + cisplatin in first-line induction. Overall survival results followed the same trend as PFS. Conclusion: The model suggests that treatment-sequencing strategies starting with a bevacizumab-based combination in first line yield better survival outcomes than those starting with pemetrexed-based combinations, a result that is attributable to the possibility of one further line of treatment with first-line bevacizumab-based treatment sequences.

Second-line cabozantinib versus nivolumab in advanced renal cell carcinoma: Systematic review and indirect treatment comparison

BACKGROUND Nivolumab and cabozantinib, two new treatment options for previously-treated advanced/metastatic renal cell carcinoma (aRCC), have recently been approved. METHODS Two independent reviewers performed study selection, data extraction, and risk of bias assessment. Indirect treatment comparisons were carried out by directly assessing HR differences and statistical modeling of Kaplan-Meier curves from these two trials. RESULTS Publications identified showed that no head-to-head comparisons had been carried out. Two indirect treatment comparisons used agreed that there was no significant difference in OS between cabozantinib and nivolumab and that cabozantinib significantly improved PFS compared to nivolumab. CONCLUSIONS The field of aRCC treatments is evolving rapidly, creating opportunities for individualized treatments and challenges for clinicians to keep up with the evidence. In lieu of availability of direct comparisons of all options, advanced modeling results presented herein can help to inform and improve personalized treatments.

Cost-effectiveness comparison of cabozantinib with everolimus, axitinib, and nivolumab in the treatment of advanced renal cell carcinoma following the failure of prior therapy in England

Purpose The aim of this study was to compare the cost-effectiveness of cabozantinib with the standard of care in England in adult patients with advanced renal cell carcinoma (aRCC), following prior vascular endothelial growth factor receptor (VEGFR)-targeted therapy. Methods We developed a partitioned-survival model with three health states to assess the cost-effectiveness of cabozantinib and its comparators. The model time horizon was 30 years. Efficacy and safety data were derived from pivotal clinical trials (METEOR: NCT01865747, CheckMate025: NCT01668784, and AXIS: NCT00678392). METEOR data were used for a direct comparison of cabozantinib and everolimus. Cabozantinib and nivolumab were compared indirectly, whereas equal efficacy for axitinib and everolimus was assumed based on a previously published expert opinion. For all efficacy endpoints, the best-fitting log-logistic or fractional polynomial curves were used to estimate outcomes. Utilities were converted from the 5-level EQ-5D version instrument applied during the METEOR study for specific health states. Reductions in utility scores due to adverse events were applied. English costs (eg, drug prices) and resource use (eg, visit to consultant) data were used. Results The total treatment cost was estimated to be 84,136 Great British Pounds (GBP) per patient treated with cabozantinib. The health gains were 2.26 life-years (LYs) and 1.78 quality-adjusted LYs (QALYs). The incremental cost-effectiveness ratios (ICERs) versus axitinib and everolimus were 98,967 GBP/QALY and 137,450 GBP/QALY, respectively. Cabozantinib was less costly and more effective than nivolumab; the incremental cost was −6,742 GBP and the QALY difference was 0.18. Conclusion Treatment with cabozantinib was more effective than treatment with axitinib or everolimus but was associated with higher total costs. When compared with nivolumab, cabozantinib represents an efficient option with nominally better efficacy and lower costs.

Rapid Relative Effectiveness Assessment of Pharmaceuticals: Transferability and Completeness of Information Derived From Global Value Dossiers To Complete A Eunethta Submission

of the HTA process in Japan, which is excluded from this analysis. NICE, PBAC and the SMC all require the number of patients with the indicated disease and a clear statement of patient numbers eligible for treatment per year for 5 years. Beyond this, the requirements of the Australian PBC and the SMC were similar, specifying prevalence, incidence and mortality data, whereas NICE requires a measure of disease burden (not clearly defined) and life expectancy among those with the disease. The epidemiology requirements did not differ by disease area. ConClusions: HTA bodies stipulate the inclusion of epidemiological data to estimate economic impact of interventions. Some requirements are common to all agencies, but there are also some important differences. Specific epidemiological data needs for individual agencies must be considered by drug developers when planning and gathering information for HTA submissions.

Societal savings in patients with advanced non-squamous non-small-cell lung cancer receiving bevacizumab-based versus non-bevacizumab-based treatments in France, Germany, Italy, and Spain.

Background The purpose of this study was to investigate the savings accrued using bevacizumab-based treatment for non-small-cell lung cancer from the societal perspective, taking only public costs into account, in France, Germany, Italy, and Spain. Methods Societal costs were estimated by collecting and analyzing labor costs, carer costs, sickness benefits, disability benefits, and home care benefits. Cost inputs were derived from publicly available databases or from the published literature. Expert opinion was only used if no other source was available. Efficacy data from two randomized clinical trials were used. The time horizon in the health economic model was lifetime. Efficacy and costs were discounted by 3.5%. All main model parameters were tested in deterministic and probabilistic sensitivity analyses. Results Mean incremental savings to society per patient ranged from €2277 in Italy to €4461 in Germany. The results were most sensitive to the change in proportion of patients working fulltime and the proportion of patients who were able to return to work. Conclusion This analysis shows that bevacizumab-based treatment in non-small-cell lung cancer is associated with more savings to society compared to standard chemotherapy in terms of increased productivity and decreased social benefits paid to patients who are able to work in France, Germany, Italy, and Spain.