Dataset Information

An Economic Evaluation of Pembrolizumab Versus Other Adjuvant Treatment Strategies for Resected High-Risk Stage III Melanoma in the USA.

ABSTRACT:

Background and objective

Over the past 5 years, adjuvant treatment options for surgically resected stage III melanoma have expanded with the introduction of several novel immune checkpoint inhibitors and targeted therapies. Pembrolizumab, a programmed cell death protein 1 inhibitor, received US Food and Drug Administration approval in 2019 for resected high-risk stage III melanoma based on significantly longer recurrence-free survival versus placebo. This study evaluated the cost-effectiveness of pembrolizumab versus other adjuvant treatment strategies for resected high-risk stage III melanoma from a US health system perspective.

Methods

A Markov cohort-level model with four states (recurrence-free, locoregional recurrence, distant metastases, death) estimated costs and quality-adjusted life-years (QALYs) for pembrolizumab versus routine observation and other adjuvant comparators: ipilimumab in the overall population; and dabrafenib?+?trametinib in the BRAF-mutation positive (BRAF+) subgroup. Transition probabilities starting from recurrence-free were estimated through parametric multi-state modeling based on phase 3 KEYNOTE-054 (NCT02362594) trial data for pembrolizumab and observation, and network meta-analyses for other comparators. Post-recurrence transitions were modeled based on electronic medical records data and trials in advanced/metastatic melanoma. Utilities were derived using quality-of-life data from KEYNOTE-054 and literature. Costs of treatment, adverse events, disease management, and terminal care were included.

Results

Over a lifetime, pembrolizumab, ipilimumab, and observation were associated with QALYs of 9.24, 7.09, and 5.95 and total costs of $511,290, $992,721, and $461,422, respectively (2019 US dollars). Pembrolizumab was thus dominant (less costly, more effective) versus ipilimumab, with an incremental cost-effectiveness ratio of $15,155/QALY versus observation. In the BRAF+ subgroup, pembrolizumab dominated dabrafenib?+?trametinib and observation, decreasing costs by $62,776 and $11,250 and increasing QALYs by 0.93 and 3.10 versus these comparators, respectively. Results were robust in deterministic and probabilistic sensitivity analyses.

Conclusions

As adjuvant treatment for resected stage III melanoma, pembrolizumab was found to be dominant and therefore cost-effective compared with the active comparators ipilimumab and dabrafenib?+?trametinib. Pembrolizumab increased costs relative to observation in the overall population, with sufficient incremental benefit to be considered cost-effective based on typical willingness-to-pay thresholds.

SUBMITTER: Bensimon AG

PROVIDER: S-EPMC7311503 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

An Economic Evaluation of Pembrolizumab Versus Other Adjuvant Treatment Strategies for Resected High-Risk Stage III Melanoma in the USA.

Bensimon Arielle G AG Zhou Zheng-Yi ZY Jenkins Madeline M Song Yan Y Gao Wei W Signorovitch James J Krepler Clemens C Scherrer Emilie E Wang Jingshu J Aguiar-Ibáñez Raquel R

Clinical drug investigation 20200701 7

<h4>Background and objective</h4>Over the past 5 years, adjuvant treatment options for surgically resected stage III melanoma have expanded with the introduction of several novel immune checkpoint inhibitors and targeted therapies. Pembrolizumab, a programmed cell death protein 1 inhibitor, received US Food and Drug Administration approval in 2019 for resected high-risk stage III melanoma based on significantly longer recurrence-free survival versus placebo. This study evaluated the cost-effecti ...[more]

PMID: 32418051

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Project description:BackgroundAdjuvant pembrolizumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) versus placebo in the phase 3 KEYNOTE-716 study of resected stage IIB or IIC melanoma. At the prespecified third interim analysis (data cut-off, January 4, 2022), the HR for RFS in the overall population was 0.64 (95% CI, 0.50 to 0.84) and the HR for DMFS was 0.64 (95% CI, 0.47 to 0.88). We present a post hoc analysis of efficacy by subtypes defined by histopathologic characteristics.MethodsPatients aged ≥12 years with newly diagnosed, resected stage IIB or IIC melanoma were randomly assigned (1:1) to pembrolizumab 200 mg every 3 weeks (2 mg/kg up to 200 mg for pediatric patients) or placebo. The primary end point was RFS per investigator review; DMFS per investigator review was secondary. Subgroups of interest were melanoma subtype (nodular vs non-nodular), tumor thickness (≤4 mm vs >4 mm), presence of ulceration (yes vs no), mitotic rate (<5 per mm2 (median) vs ≥5 per mm2), and presence of tumor-infiltrating lymphocytes (TILs; absent vs present).ResultsBetween September 23, 2018, and November 4, 2020, 976 patients were assigned to pembrolizumab (n=487) or placebo (n=489). Median follow-up was 27.4 months (range, 14.0-39.4). The HR (95% CI) for RFS was 0.54 (0.37 to 0.79) for nodular and 0.77 (0.53 to 1.11) for non-nodular melanoma; 0.57 (0.37 to 0.89) for thickness ≤4 mm and 0.69 (0.50 to 0.96) for >4 mm; 0.66 (0.50 to 0.89) for ulceration and 0.57 (0.32 to 1.03) for no ulceration; 0.57 (0.35 to 0.92) for mitotic rate <5 per mm2 and 0.57 (0.40 to 0.80) for ≥5 per mm2; and 0.89 (0.52 to 1.54) for TILs absent and 0.51 (0.34 to 0.76) for TILs present. DMFS results were similar. In a Cox multivariate analysis, treatment arm, tumor thickness, and mitotic rate were significant independent factors for RFS, and treatment arm and mitotic rate were significant independent factors for DMFS.ConclusionsIn this post hoc analysis, the benefit of pembrolizumab was largely consistent with the overall study population regardless of histopathologic characteristics. These results support the use of adjuvant pembrolizumab in patients with resected stage IIB or IIC melanoma.Trial registration numberClinicalTrials.gov, NCT03553836.

Project description:BackgroundOn the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had undergone complete resection of stage III melanoma.MethodsAfter patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months for up to 3 years or until disease recurrence or an unacceptable level of toxic effects occurred. Recurrence-free survival was the primary end point. Secondary end points included overall survival, distant metastasis-free survival, and safety.ResultsAt a median follow-up of 5.3 years, the 5-year rate of recurrence-free survival was 40.8% in the ipilimumab group, as compared with 30.3% in the placebo group (hazard ratio for recurrence or death, 0.76; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). The rate of overall survival at 5 years was 65.4% in the ipilimumab group, as compared with 54.4% in the placebo group (hazard ratio for death, 0.72; 95.1% CI, 0.58 to 0.88; P=0.001). The rate of distant metastasis-free survival at 5 years was 48.3% in the ipilimumab group, as compared with 38.9% in the placebo group (hazard ratio for death or distant metastasis, 0.76; 95.8% CI, 0.64 to 0.92; P=0.002). Adverse events of grade 3 or 4 occurred in 54.1% of the patients in the ipilimumab group and in 26.2% of those in the placebo group. Immune-related adverse events of grade 3 or 4 occurred in 41.6% of the patients in the ipilimumab group and in 2.7% of those in the placebo group. In the ipilimumab group, 5 patients (1.1%) died owing to immune-related adverse events.ConclusionsAs adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo. There were more immune-related adverse events with ipilimumab than with placebo. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00636168 , and EudraCT number, 2007-001974-10 .).

Dataset Information

An Economic Evaluation of Pembrolizumab Versus Other Adjuvant Treatment Strategies for Resected High-Risk Stage III Melanoma in the USA.

Background and objective

Methods

Results

Conclusions

Publications

An Economic Evaluation of Pembrolizumab Versus Other Adjuvant Treatment Strategies for Resected High-Risk Stage III Melanoma in the USA.

Similar Datasets

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