Dataset Information

Frontline BRAF Testing-Guided Treatment for Advanced Melanoma in the Era of Immunotherapies: A Cost-Utility Analysis Based on Long-term Survival Data.

ABSTRACT:

Importance

The effectiveness of immune checkpoint inhibitors (ICIs) and BRAF and MEK inhibitors has improved advanced melanoma recovery. However, it is unknown whether these novel therapies are cost-effective for newly diagnosed advanced melanoma with unknown BRAF status.

Objective

To compare the cost-utility of these novel agents and their combinations with or without BRAF gene testing guidance for treating newly diagnosed advanced melanoma with unknown BRAF status.

Design and setting

A decision-analytic model was adopted to project the outcomes of 8 strategies containing different ICIs and BRAF and MEK inhibitors for newly diagnosed advanced melanoma with unknown BRAF pathogenic variant status. The key clinical data were derived from the CheckMate 067, KEYNOTE-006, COMBI-d, and COMBI-v trials, and the cost and health preference data were derived from the literature. Costs were estimated from the US payer perspective.

Main outcomes and measures

Costs, quality-adjusted life-years (QALYs), incremental cost-utility ratio (ICUR), and incremental net health benefits were calculated. Subgroup, 1-way, and probabilistic sensitivity analyses were performed.

Results

Of the 8 competing strategies, nivolumab plus ipilimumab without patient selection based on BRAF pathogenic variant testing yielded the most significant health outcome, and the nivolumab strategy was the cheapest option. The nivolumab, pembrolizumab, and nivolumab plus ipilimumab strategies formed the cost-effective frontier, which showed the ordered ICURs were $8593 (SD, $592 995)/QALY for pembrolizumab vs nivolumab and $125 593 (SD, $5 751 223)/QALY for nivolumab plus ipilimumab vs pembrolizumab. Other strategies, including the BRAF testing-guided strategies (BRAF pathogenic variant testing followed by corresponding regimens for BRAF wild and pathogenic variant tumors), were dominated or extended dominated. The most influential parameters were the treatment efficacy of these new regimens.

Conclusions and relevance

For newly diagnosed advanced melanoma with unknown BRAF pathogenic variant status, nivolumab plus ipilimumab and pembrolizumab strategies are likely to be the most cost-effective options. BRAF and MEK inhibitors might be productively placed in a second-line setting after BRAF pathogenic variant is confirmed.

SUBMITTER: Wu B

PROVIDER: S-EPMC7376469 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17%. Randomized controlled trials of recent US Food and Drug Administration-approved immune checkpoint inhibitors-pembrolizumab (PEM), nivolumab (NIVO), and ipilumumab (IPI)-demonstrate improved patient outcomes, but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear. To inform policy makers about the value of these treatments, we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma. Materials and Methods We developed Markov models by using a US-payer perspective and lifetime horizon to estimate costs (2016 US$) and quality-adjusted life years (QALYs) for treatment sequences with first-line NIVO, IPI, NIVO + IPI, PEM every 2 weeks, and PEM every 3 weeks. Health states were defined for initial treatment, first and second progression, and death. Rates for drug discontinuation, frequency of adverse events, disease progression, and death obtained from randomized phase III trials were used to determine the likelihood of transition between states. Deterministic and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. Results PEM every 3 weeks followed by second-line IPI was both more effective and less costly than dacarbazine followed by IPI then NIVO, or IPI followed by NIVO. Compared with the first-line dacarbazine treatment strategy, NIVO followed by IPI produced an incremental cost effectiveness ratio of $90,871/QALY, and first-line NIVO + IPI followed by carboplatin plus paclitaxel chemotherapy produced an incremental cost effectiveness ratio of $198,867/QALY. Conclusion For patients with treatment-naive BRAF wild-type advanced melanoma, first-line PEM every 3 weeks followed by second-line IPI or first-line NIVO followed by second-line IPI are the most cost-effective, immune-based treatment strategies for metastatic melanoma.