Economic Evaluation of Nivolumab Plus Ipilimumab Combination as First-Line Treatment for Patients with Advanced Melanoma in Canada.
Ontology highlight
ABSTRACT:
SUBMITTER: Quon PL
PROVIDER: S-EPMC6710483 | BioStudies | 2019-01-01
REPOSITORIES: biostudies
Similar Datasets
Project description:BACKGROUND:Escalating healthcare costs are necessitating the practice of value-based oncology. It is crucial to critically evaluate the economic impact of influential but expensive therapies such as immune checkpoint inhibitors (ICIs). To date, no systematic assessment of the cost-effectiveness (CE) of ICIs has been performed. METHODS:PRISMA-guided systematic searches of the PubMed database were conducted. Studies of head/neck (n = 3), lung (n = 5), genitourinary (n = 4), and melanoma (n = 8) malignancies treated with ICIs were evaluated. The reference willingness-to-pay (WTP) threshold was $100,000/QALY. RESULTS:Nivolumab was not cost-effective over chemotherapy for recurrent/metastatic head/neck cancers (HNCs). For non-small cell lung cancer (NSCLC), nivolumab was not cost-effective for a general cohort, but increased PD-L1 cutoffs resulted in CE. Pembrolizumab was cost-effective for both previously treated and newly-diagnosed metastatic NSCLC. For genitourinary cancers (GUCs, renal cell and bladder cancers), nivolumab and pembrolizumab were not cost-effective options. Regarding metastatic/unresected melanoma, ipilimumab monotherapy is less cost-effective than nivolumab, nivolumab/ipilimumab, and pembrolizumab. The addition of ipilimumab to nivolumab monotherapy was not adequately cost-effective. Pembrolizumab or nivolumab monotherapy offered comparable CE profiles. CONCLUSIONS:With limited data and from the reference WTP, nivolumab was not cost-effective for HNCs. Pembrolizumab was cost-effective for NSCLC; although not the case for nivolumab, applying PD-L1 cutoffs resulted in adequate CE. Most data for nivolumab and pembrolizumab in GUCs did not point towards adequate CE. Contrary to ipilimumab, either nivolumab or pembrolizumab is cost-effective for melanoma. Despite these conclusions, it cannot be overstated that careful patient selection is critical for CE. Future publication of CE investigations and clinical trials (along with longer follow-up of existing data) could substantially alter conclusions from this analysis.
2018-01-01 | S-EPMC6251215 | BioStudies
Project description:Background:Immune checkpoint inhibitors (ICIs) are effective for advanced renal-cell carcinoma (aRCC) but can increase costs. This study compares the efficacy, safety and cost-effectiveness of ICIs for newly diagnosed aRCC patients in the first-line setting. Methods:Trials evaluating ICI regimens as first-line treatment for newly diagnosed aRCC were searched and included. A network meta-analysis (NMA) was conducted, and a cost-effectiveness analysis was performed from the US payer's perspective. The key outcomes were overall survival (OS) and progression-free survival (PFS) in the NMA, and quality-adjusted life years (QALYs), costs and the incremental cost-effectiveness ratio (ICER) in the cost-effectiveness analysis. Results:Four randomized controlled trials (RCTs) involving 3758 patients receiving first-line ICIs treatment were analyzed. The NMA showed that pembrolizumab plus axitinib was ranked higher than the other three ICI regimens and sunitinib in the overall population. Nivolumab plus ipilimumab and pembrolizumab plus axitinib achieved more health benefits than the other ICI regimens and sunitinib in programmed death ligand 1 (PD-L1)-positive and negative tumors, respectively. Among the four ICI regimens, only the ICERs of nivolumab plus ipilimumab over sunitinib were lower than the willingness-to-pay threshold ($150,000/QALY) in the overall and PD-L1-positive populations, and none of four ICI regimens were lower than $150,000/QALY in PD-L1-negative populations. Conclusions:The NMA and cost-effectiveness analysis revealed that nivolumab plus ipilimumab is the most favorable first-line treatment for PD-L1-positive aRCC compared with other ICI regimens and sunitinib. Pembrolizumab plus axitinib is likely to be an alternative for PD-L1-negative aRCC due to its more favorable health advantages.
2020-01-01 | S-EPMC7436799 | BioStudies
Project description:Importance:Checkpoint inhibitor combination therapy represents a major advance in the first-line treatment of advanced renal cell carcinoma. Pembrolizumab-axitinib and nivolumab-ipilimumab have become standard of care options after demonstrating clinical efficacy against sunitinib in separate phase 3 trials. The cost-effectiveness of these regimens is unknown. Objective:To evaluate the cost-effectiveness of pembrolizumab-axitinib and nivolumab- ipilimumab in the first-line treatment of advanced renal cell carcinoma. Design, Setting, and Participants:For this economic evaluation, a primary microsimulation model was developed and run between August and December 2019. Separate analyses were conducted for an intermediate- and poor-risk patient population (base case) and a favorable-risk population (exploratory analysis) because prognosis is known to differ between risk groups; 100?000 patients with advanced renal cell carcinoma were simulated in each treatment arm. Survival, treatment regimens, and other relevant conditions were based on data from the phase 3 KEYNOTE-426 and CheckMate214 clinical trials. The study perspective was the US health care sector. Main Outcomes and Measures:An incremental cost-effectiveness ratio was calculated for each of the 2 analyses and compared with a willingness-to-pay threshold of $100?000 per quality-adjusted life-year (QALY). Results:Pembrolizumab-axitinib was estimated to add 0.60 QALYs compared with nivolumab-ipilimumab in the base case analysis (3.66 vs 3.05 QALYs) and 0.25 QALYs compared with nivolumab-ipilimumab in the exploratory analysis (4.55 vs 4.30 QALYs), and was more costly (base case analysis: $562?927 vs $458?961; exploratory analysis: $589?035 vs $470?403). The incremental cost-effectiveness ratio was $172?532 per QALY in the base case analysis and $468?682 per QALY in the exploratory analysis. One-way sensitivity analyses revealed that the base case model was most sensitive to first-line drug prices (incremental cost-effectiveness ratio at upper limit of nivolumab price and lower limits of axitinib and pembrolizumab prices: $89?983, $102?287, and $114?943 per QALY, respectively). The exploratory analysis model was most sensitive to overall survival rates (incremental cost-effectiveness ratio at lower limit of pembrolizumab-axitinib rate and upper limit of nivolumab-ipilimumab rate: $278?644 and $285?684 per QALY, respectively). Conclusions and Relevance:The findings suggest that pembrolizumab-axitinib treatment is associated with greater QALYs compared with nivolumab/ipilimumab treatment in patients with advanced renal cell carcinoma but may not be cost-effective. Price reductions may make the cost of pembrolizumab-axitinib proportional to its clinical value and less financially burdensome to the US health care system.
2020-01-01 | S-EPMC7557509 | BioStudies
Project description:The approval of new immunotherapies has dramatically changed the treatment landscape of metastatic melanoma. These survival gains come with trade-offs in side effects and costs, as well as important considerations for third-party payer systems, physicians, and patients.To develop a Markov model to determine the cost-effectiveness of nivolumab, ipilimumab, and nivolumab-ipilimumab combination as firstline therapy in metastatic melanoma, while accounting for differential effectiveness in programmed death-ligand 1 (PD-L1) positive and negative patients.A 3-state Markov model (PD-L1 positive stable disease, PD-L1 negative stable disease, and progression and/or death) was developed using a U.S. societal perspective with a lifetime time horizon of 14.5 years. Transition probabilities were calculated from progression-free (PF) survival data reported in the CheckMate-067 trial. Costs were expressed in 2015 U.S. dollars and were determined using national sources. Adverse event (AE) management was determined using immune-related AE (irAE) data from CheckMate-067, irAE management guides for nivolumab and ipilimumab, and treatment guidelines. Utilities were obtained from published literature, using melanoma-specific studies when available, and were weighted based on incidence and duration of irAEs. Base case, one-way sensitivity, and probabilistic sensitivity analyses were conducted.Nivolumab-ipilimumab combination therapy was not the cost-effective choice ($454,092 per PF quality-adjusted life-year [QALY]) compared with nivolumab monotherapy in a base case analysis at a willingness-to-pay threshold of $100,000 per PFQALY. Combination therapy and nivolumab monotherapy were cost-effective choices compared with ipilimumab monotherapy. PD-L1 positive status, utility of nivolumab and combination therapy, and medication costs contributed the most uncertainty to the model. In a population of 100% PD-L1 negative patients, nivolumab was still the optimal treatment, but combination therapy had an improved incremental cost-effectiveness ratio (ICER) of $295,903 per PFQALY. Combination therapy became dominated by nivolumab, when 68% of the sample was PD-L1 positive. In addition, the cost of ipilimumab would have to decrease to < $21,555 per dose for combination therapy to have an ICER < $100,000 per PFQALY and to < $19,151 (a 42% reduction) to be more cost-effective than nivolumab monotherapy.Nivolumab-ipilimumab combination therapy was not cost-effective compared with nivolumab monotherapy, which was the most cost-effective option. Professionals in managed care settings should consider the pharmacoeconomic implications of these new immunotherapies as they make value-based formulary decisions, and future cost-effectiveness studies are completed.No funding supported this study. Merino was a contractor with EMD Serono at the time of this study but does not have any conflicts of interest and did not receive any funding related to this study. All other authors have no financial disclosures and no conflicts of interest. All the authors contributed to the study concept and design. Tran, McDowell, and Barcelon took the lead in data collection, along with Oh, Keyvani, and Merino. All authors except Merino contributed to data interpretation. The manuscript was written by Oh, Tran, McDowell, and Wilson and revised by Oh, Tran, McDowell, Wilson, and Keyvani. This analysis was presented at Academy of Managed Care Pharmacy Managed Care & Specialty Pharmacy Annual Meeting 2016, April 19-22, 2016, in San Francisco, California, and at the International Society for Pharmacoeconomics and Outcomes Research Annual International Meeting, May 21-25, 2016, in Washington DC.
2017-01-01 | S-EPMC5960988 | BioStudies
Project description:Background: The CheckMate 227 trial has indicated that nivolumab plus ipilimumab compared with chemotherapy significantly increases long-term survival in the first-line setting of advanced non-small-cell lung cancer (NSCLC). Methods: A Markov model was built to estimate the cost and effectiveness of nivolumab plus ipilimumab vs. chemotherapy as the first-line therapy in patients with advanced NSCLC based on outcomes data from the CheckMate 227 trial. We calculated the cost and health outcomes at a willingness-to-pay (WTP) threshold of $150,000 per quality adjusted life year (QALY) in populations with different programmed death ligand 1 (PD-L1) expression levels (?50, ?1, and <1%) or a high tumor mutational burden (TMB) (?10 mutations per megabase). Sensitivity analysis were used to test the model stability. Results: The outcomes showed that the incremental costs and QALYs by using nivolumab plus ipilimumab were $124180.76 and 1.16, $70951.42 and 0.53, $144093.63 and 0.83 for the advanced NSCLC patients with a PD-L1 expression ?50%, ?1%, and <1%, which led to an incremental cost-effective ratio (ICER) of $107403.72, $133732.20, and $172589.15 per QALY, respectively. For patients with a high TMB, nivolumab plus ipilimumab contributed an extra 2.04 QALYs at a cost of $69182.50 per QALY. Conclusion: Nivolumab plus ipilimumab as first-line therapy makes a better cost-effective strategy than chemotherapy in advanced NSCLC patients with PD-L1 expression levels ?50% and ?1% or a high TMB, at a willingness-to-pay threshold of $150,000 per QALY, but not in the patients with a PD-L1 expression <1%.
2020-01-01 | S-EPMC7507990 | BioStudies
Project description:We aimed to compare and rank the effects of 9 immune checkpoint inhibitor-related therapies for treating advanced melanoma.We searched Pubmed, Cochrane databases, Web of Science, and ClinicalTrials.gov for randomized controlled trials of the immune checkpoint inhibitor-related treatments for advanced melanoma. Analysis was done on a Bayesian framework.Twelve trials including 5413 patients were identified. Ipilimumab plus nivolumab, nivolumab, and pembrolizumab were significantly more efficacious for progression-free survival (PFS) than ipilimumab (hazard ratio [HR], 0.38, 0.50, and 0.58, respectively), ipilimumab plus chemotherapy (0.45, 0.60, and 0.70, respectively), or ipilimumab plus sargramostim (0.44, 0.57, and 0.67, respectively). Ipilimumab plus gp100 was significantly less efficacious for PFS than the remaining eight immune checkpoint inhibitor-related strategies. Pembrolizumab was significantly more efficacious than ipilimumab and ipilimumab plus gp100 (HR, 0.66, and 0.64, respectively) in improving overall survival (OS). Nivolumab significantly improved OS over tremelimumab (HR, 0.48). Ipilimumab plus sargramostim was ranked the second most effective strategy in terms of OS and well tolerated. Nivolumab and pembrolizumab showed the best profile of acceptability, with significantly less high-grade adverse events than ipilimumab (odds ratio [OR], 0.49 and 0.50, respectively), tremelimumab (0.21 and 0.21, respectively), ipilimumab plus chemotherapy (0.13 and 0.13, respectively), or ipilimumab plus nivolumab (0.15 and 0.15, respectively).Nivolumab, pembrolizumab and ipilimumab plus sargramostim might be optimum treatments for advanced melanoma because they have the most favorable balance between benefits and acceptability. Ipilimumab plus nivolumab is the most effective in prolonging PFS, but is far more toxic than nivolumab and pembrolizumab.
1000-01-01 | S-EPMC5663542 | BioStudies
Project description:BACKGROUND:Nivolumab with ipilimumab (the Regimen) is the first immuno-oncology combination treatment to demonstrate long-term clinical benefit for advanced melanoma patients. We evaluated the cost effectiveness of the Regimen in this population, with and without the availability of overall survival (OS) data. METHODS:A partitioned survival model and a Markov state-transition model were developed to estimate the lifetime costs and benefits of the Regimen versus ipilimumab. These models were built with and without the availability of OS data, as only progression-free survival data were available from the head-to-head, phase III trial against ipilimumab at the time of the National Institute for Health and Care Excellence (NICE) submission. Patient utilities and resource use data were sourced from trial data or the literature. RESULTS:Incremental cost-effectiveness ratios (ICERs) and absolute costs were similar between the models with and without OS data, but the model with OS data generated more than 1 additional quality-adjusted life-year (QALY) across both treatment arms. In both models, based on list prices, the Regimen was the most cost-effective treatment. CONCLUSIONS:The analyses show that the Regimen is a cost-effective treatment for advanced melanoma patients in England, and methods to overcome the lack of OS can give reasonable estimates of QALYs gained and ICERs.
2019-01-01 | S-EPMC6393277 | BioStudies
Project description:We conducted a network meta-analysis in order to compare different strategies for managing melanoma patients. Electronic databases were searched for eligible randomized trials that compared different strategies in efficacy and tolerability. Five interventions were associated with a significant improvement in PFS over chemotherapy (all HR < 1): Ipilimumab, Tremelimumab, Nivolumab, Pembrolizumab 2 mg/kg and Ipilimumab + Nivolumab. Three interventions exhibited significantly improved OS results over chemotherapy (all HR < 1): Ipilimumab, Nivolumab and Ipilimumab + Chemotherapy. Four interventions were superior to chemotherapy in CR and PR (all OR > 1): Nivolumab, Pembrolizumab 10 mg/kg, Pembrolizumab 2 mg/kg and Ipilimumab + Nivolumab. However, the other seven interventions were associated with an increased risk of pruritus compared to chemotherapy (all OR > 1). Ipilimumab, Tremelimumab, Ipilimumab + Nivolumab and Ipilimumab + Chemotherapy might result in a higher risk of diarrhea compared to chemotherapy (all OR > 1). Immune checkpoint therapy or combined interventions might be more effective than chemotherapy for managing melanoma patients. However, chemotherapy appears to be more tolerable than these combined strategies with respect to adverse events.
2016-01-01 | S-EPMC5348360 | BioStudies
Project description:Over the last 18 months, 3 immunotherapy combination regimens (ipilimumab + nivolumab, pembrolizumab + axitinib, and axitinib + avelumab) were approved by the US Food and Drug Administration for the first-line treatment of metastatic renal cell carcinoma (mRCC), making selection of the optimal first-line treatment regimen very challenging. As of April 2020, preferred first-line treatment options for mRCC are pembrolizumab + axitinib and ipilimumab + nivolumab, based on the improvement in overall survival and progression-free survival compared to sunitinib, as observed in pivotal phase III clinical trials. Because the combination of 2 drugs is typically more toxic than a monotherapy, careful attention must be given to overlapping toxicities. The pembrolizumab + axitinib combination led to grade ?3 adverse events in 75.8% of patients (vs 70.6% in the sunitinib group), while grade ?3 adverse events were less frequent in the nivolumab + ipilimumab group compared to the sunitinib group. Discontinuation rates due to toxicity were 10.7% for pembrolizumab + axitinib (both drugs), 22% for ipilimumab + nivolumab and were comparable with sunitinib in both studies (13.9% and 12%, respectively). The combination of pembrolizumab + axitinib may have immune-modulating functions that may provide clinical benefit without the additional toxicity observed with ipilimumab + nivolumab. In addition, this tyrosine kinase inhibitor + immune checkpoint combination should have faster treatment response in patients with larger disease burden or in more symptomatic patients, which makes this combination an excellent choice for the first-line treatment regimen for mRCC. These combinations have proven to be tolerable, though long-term results are still lacking. As treatment options for mRCC are rapidly expanding, immunotherapy combinations could potentially change the treatment paradigm, with the ultimate goal of prolonging life and eventually curing mRCC.
2020-01-01 | S-EPMC7443011 | BioStudies
Project description:<h4>Importance</h4>Since 2011, immune checkpoint inhibitors (ICIs) have been effective treatment options for advanced melanoma. Little is known about how risks of immune-related adverse events (irAEs) vary by ICIs.<h4>Objective</h4>To compare the risk of irAEs across different treatment regimens for advanced melanoma using network meta-analysis.<h4>Data sources</h4>PubMed/MEDLINE, Embase, Web of Science, and Scopus were searched for all randomized clinical trial (RCT) articles published from January 1, 2010, through June 30, 2019.<h4>Study selection</h4>Studies included phases 2 and 3 RCTs in the treatment of advanced melanoma that compared ICIs (ipilimumab, nivolumab, and pembrolizumab) with chemotherapy drugs (eg, dacarbazine, carboplatin, and paclitaxel) or different ICI regimens.<h4>Data extraction and synthesis</h4>Different treatment regimens were compared using bayesian network meta-analysis with Markov chain Monte Carlo simulation with noninformative prior distribution and random-effects generalized linear models.<h4>Main outcomes and measures</h4>Primary outcomes were the cumulative incidence of any irAEs (regardless of severity) and severe irAEs (grades 3-5). Based on the pooled odds ratios (ORs) and 95% credible intervals (95% CrI), the probability of being associated with the lowest irAE risks was estimated for each treatment regimen.<h4>Results</h4>Nine RCTs with 8 different treatment regimens for advanced melanoma and involving a total of 5051 patients were included. Overall, the 3 ICI treatment regimens associated with the lowest risk of any or severe irAEs were pembrolizumab, 2 mg/kg, every 3 weeks; nivolumab, 3 mg/kg, every 2 weeks; and pembrolizumab, 10 mg/kg, every 3 weeks. Compared with ipilimumab, 10 mg/kg, every 3 weeks, only nivolumab, 3 mg/kg, every 2 weeks, was associated with a decreased risk for any irAEs (OR, 0.34; 95% CrI, 0.13-0.94). A decreased risk for severe irAEs was observed for ipilimumab, 3 mg/kg, every 3 weeks (OR,?0.35; 95% CrI,?0.14-0.74); pembrolizumab, 10 mg/kg, every 2 weeks (OR,?0.22; 95% CrI,?0.05-0.95) and 10 mg/kg every 3 weeks (OR,?0.20; 95% CrI,?0.06-0.68); and nivolumab, 3 mg/kg, every 2 weeks (OR,?0.20; 95% CrI,?0.07-0.48) compared with ipilimumab, 10 mg/kg, every 3 weeks. An increased risk for severe irAEs was associated with nivolumab, 1 mg/kg, every 3 weeks combined with ipilimumab, 3 mg/kg, every 3 weeks compared with other ICI regimens (ORs ranging from?4.09 [95% CrI, 1.73-10.99] to 7.40 [95% CrI, 1.12-49.29]) except ipilimumab, 10 mg/kg, every 3 weeks.<h4>Conclusions and relevance</h4>These findings suggest that for patients with advanced melanoma at high risk of irAEs, pembrolizumab, 2 mg/kg, every 3 weeks, nivolumab, 3 mg/kg, every 2 weeks, and pembrolizumab, 10 mg/kg, every 3 weeks may be the preferred treatment regimens (with respect to irAE risks) among the ICI regimens reported, whereas ipilimumab, 10 mg/kg, every 3 weeks alone and nivolumab, 1 mg/kg, every 3 weeks combined with ipilimumab, 3 mg/kg, every 3 weeks should be used with caution. A network analysis may be valuable for clinical decision-making when evidence from head-to-head comparisons is lacking.
2020-01-01 | S-EPMC7097702 | BioStudies