Dataset Information

Cost-effectiveness of Nivolumab-Ipilimumab Combination Therapy for the Treatment of Advanced Non-Small Cell Lung Cancer.

ABSTRACT:

Importance

Treatment with nivolumab-ipilimumab combination therapy was found to improve overall survival compared with chemotherapy among patients with advanced non-small cell lung cancer (NSCLC) in the CheckMate 227 clinical trial. However, these drugs are substantially more expensive than chemotherapy and, given the high incidence of advanced NSCLC, the incorporation of dual immune checkpoint inhibitors into the standard of care could have substantial economic consequences.

Objective

To assess whether nivolumab-ipilimumab combination therapy is a cost-effective first-line treatment for patients with advanced NSCLC.

Design, setting, and participants

This economic evaluation designed a Markov model to compare the cost-effectiveness of nivolumab-ipilimumab combination therapy with platinum-doublet chemotherapy as first-line treatment for patients with advanced NSCLC. The Markov model was created to simulate patients with advanced NSCLC who were receiving either nivolumab-ipilimumab combination therapy or platinum-doublet chemotherapy. Transition probabilities, including disease progression, survival, and treatment toxic effects, were derived using data from the CheckMate 227 clinical trial. Costs and health utilities were obtained from published literature. Data analyses were conducted from November 2019 to September 2020.

Exposures

Nivolumab-ipilimumab combination therapy.

Main outcomes and measures

The primary study outcomes were quality-adjusted life-years (QALYs) and cost in 2020 US dollars. Cost-effectiveness was measured using an incremental cost-effectiveness ratio (ICER), with an ICER less than $100 000 per QALY considered cost-effective. Model uncertainty was assessed with 1-way and probabilistic sensitivity analyses.

Results

Treatment with nivolumab-ipilimumab combination therapy was associated with an increase in overall cost of $201 900 and improved effectiveness of 0.50 QALYs compared with chemotherapy, yielding an ICER of $401 700 per QALY. The study model was sensitive to the cost and duration of immunotherapy. Treatment with nivolumab-ipilimumab combination therapy became cost-effective when monthly treatment costs were reduced from $26 425 to $5058 (80.9% reduction) or when the maximum duration of immunotherapy was reduced from 24.0 months to 1.4 months. The model was not sensitive to assumptions about survival or programmed cell death 1 ligand 1 status. A probabilistic sensitivity analysis indicated that, at a willingness-to-pay threshold of $100 000 per QALY, nivolumab-ipilimumab combination therapy was less cost-effective than chemotherapy 99.9% of the time.

Conclusions and relevance

In this study, first-line treatment with nivolumab-ipilimumab combination therapy was not found to be cost-effective at current prices despite clinical trial data indicating that this regimen increases overall survival among patients with advanced NSCLC.

SUBMITTER: Courtney PT

PROVIDER: S-EPMC8094011 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Background:Monoclonal antibodies targeting the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) (e.g., ipilimumab [IPI]) and the programmed cell death-1 (PD1) receptor (e.g., nivolumab [NIVO]) represent significant breakthroughs in the treatment of advanced melanoma. A combination of the 2 agents has demonstrated efficacy and survival benefits over NIVO or IPI monotherapy in treating advanced melanoma. We compared melanoma-specific costs following treatment with NIVO?+?IPI, NIVO monotherapy, or IPI monotherapy from the UK and German perspectives to ascertain whether these clinical benefits resulted in a cost advantage. Methods:Patient-level resource utilization data for the three treatment cohorts were obtained from the CheckMate 067 trial (NCT01844505). All melanoma-specific resources, including drugs (index, concomitant and subsequent melanoma medications), office visits, emergency room visits, hospitalizations, lab tests, procedures and surgeries, utilized over a 48-month evaluation period after start of index treatment were included. Unit costs specific to each geography were applied from external sources. Mean costs per surviving patients were calculated for each successive 30-day period from treatment start and aggregated over the evaluation period. Results:The total per-patient costs incurred by advanced melanoma patients over the 48-month period following treatment initiation with NIVO?+?IPI were 9% lower than NIVO monotherapy (£226k vs £248k) and 3% lower compared to IPI monotherapy (£226k vs. £233k) in the UK. In Germany, the total costs incurred by NIVO?+?IPI cohort were 5% lower than NIVO monotherapy (€258k vs €271k) and 4% lower compared to IPI monotherapy (€258k vs. €268k). Drug costs accounted for >?85% of total costs. Non-drug costs were slightly higher for NIVO?+?IPI and IPI monotherapy because of higher hospitalization rates. Costs incurred on subsequent drugs post progression were about 45% and 65% lower in NIVO?+?IPI cohort compared with NIVO and IPI monotherapy cohorts respectively. Conclusions:The total costs incurred by a patient over a 48-month period following treatment initiation with NIVO?+?IPI are lower when compared with patients initiating monotherapies; further, the cost advantage is seen to be increasing over time. The clinical benefits offered by the regimen are thus supplemented by a cost advantage, as patients receiving either monotherapy treatment experience faster progression and, consequently, higher subsequent treatment costs. (Note: The cost results reported here are specific to the UK, and Germany, and may not be generalizable to other geographies).

Project description:BACKGROUND AND OBJECTIVE:The economic assessment of immuno-oncology agents in Chinese patients is limited despite a need for new therapies. Nivolumab is the first immune checkpoint inhibitor approved for the second-line treatment of non-small cell lung cancer (NSCLC) in China, and it significantly prolongs overall survival. However, considering the high cost of nivolumab, it is urgent to assess its value in China in terms of both efficacy and cost. The objective of this study was to investigate the cost-effectiveness of nivolumab vs docetaxel in the second-line setting for NSCLC patients from the Chinese healthcare system perspective. METHODS:A Markov model consisting of three health states, was designed to evaluate the lifetime cost and effectiveness of nivolumab vs docetaxel in the second-line treatment of NSCLC patients. Clinical data was derived from the CheckMate 078 phase III clinical trial, which included 504 patients predominantly from China. Parametric survival models to fit and extrapolate survival data were chosen based on clinical rationality, visual fit and statistical goodness-of-fit. Lifetime costs and health outcomes were calculated, and US$28,899 and $63,564 per quality-adjusted life-year (QALY) were selected as the willingness-to-pay (WTP) threshold values for general regions and affluent regions, respectively. One-way and probabilistic sensitivity analyses were undertaken to explore the robustness of the model. Additional subgroup analyses were performed. RESULTS:In base case analysis, Nivolumab yielded an additional 0.24 QALYs, at a cost of $93,307 per QALY. Sensitivity analyses suggested that the results to be most sensitive to the price of nivolumab per kg (mean $60.00; range $26.00-$60.00) and the mean patient weight (65 kg, range 52-78 kg). Utility values in progression-free survival state (mean 0.804; range 0.643-0.965) and overall survival hazard ratio (0.68; 97.7% CI 0.52-0.90) had moderate impact on the model results. Subgroup analyses indicated that nivolumab was most cost-effective for patients who were 65 years of age or older ($85,171/QALY), followed by female patients ($85,273/QALY) and patients with tumor PD-L1 expression at least 1% ($90,309/QALY). CONCLUSIONS:Nivolumab is unlikely to be cost-effective compared with docetaxel for patients with previously treated advanced NSCLC in China. Ensuring that nivolumab is included in the National Reimbursement Drug List (NRDL) may be a valid mean of meeting extensive treatment demands in China.

Project description:We conducted the first trial of neoadjuvant PD-1 blockade in resectable non-small cell lung cancer (NSCLC), finding nivolumab monotherapy to be safe and feasible with an encouraging rate of pathologic response. Building on these results, and promising data for nivolumab plus ipilimumab (anti-CTLA-4) in advanced NSCLC, we expanded our study to include an arm investigating neoadjuvant nivolumab plus ipilimumab. Patients with resectable stage IB (≥4 cm)-IIIA (American Joint Committee on Cancer Tumor Node Metastases seventh edition), histologically confirmed, treatment-naïve NSCLC received nivolumab 3 mg/kg intravenously plus ipilimumab 1 mg/kg intravenously 6 weeks prior to planned resection. Nivolumab 3 mg/kg was given again approximately 4 and 2 weeks preoperatively. Primary endpoints were safety and feasibility with a planned enrollment of 15 patients. Pathologic response was a key secondary endpoint. While the treatment regimen was feasible per protocol, due to toxicity, the study arm was terminated early by investigator consensus after 9 of 15 patients were enrolled. All patients received every scheduled dose of therapy and were fit for planned surgery; however, 6 of 9 (67%) experienced treatment-related adverse events (TRAEs) and 3 (33%) experienced grade ≥3 TRAEs. Three of 9 patients (33%) had biopsy-confirmed tumor progression precluding definitive surgery. Of the 6 patients who underwent resection, 3 are alive and disease-free, 2 experienced recurrence and are actively receiving systemic treatment, and one died postoperatively due to acute respiratory distress syndrome. Two patients who underwent resection had tumor pathologic complete responses (pCRs) and continue to remain disease-free over 24 months since surgery. Pathologic response correlated with pre-treatment tumor PD-L1 expression, but not tumor mutation burden. Tumor KRAS/STK11 co-mutations were identified in 5 of 9 patients (59%), of whom two with disease progression precluding surgery had tumor KRAS/STK11/KEAP1 co-mutations. Though treatment was feasible, due to toxicity the study arm was terminated early by investigator consensus. In light of this, and while the long-term disease-free status of patients who achieved pCR is encouraging, further investigation of neoadjuvant nivolumab plus ipilimumab in patients with resectable NSCLC requires the identification of predictive biomarkers that enrich for response.

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.