# Incorporating the possibility of cure into network meta-analyses: A case study from resected Stage III/IV melanoma

## TL;DR

This paper introduces a new method to analyze cancer survival data using mixture cure models in network meta-analysis, demonstrated through a melanoma case study.

## Contribution

The paper proposes a novel methodology for network meta-analysis using mixture cure models to account for long-term survival in oncology.

## Key findings

- The MCM NMA approach was successfully applied to recurrence-free survival data in resected stage III/IV melanoma.
- The method allows for the estimation of both relative and absolute survival effects while accounting for the possibility of cure.
- Key considerations for MCM NMA include data maturity, model selection, and result interpretation.

## Abstract

In many areas of oncology, cancer drugs are now associated with long-term survivorship and mixture cure models (MCM) are increasingly being used for survival analysis. The objective of this article was to propose a methodology for conducting network meta-analysis (NMA) of MCM. This method was illustrated through a case study evaluating recurrence-free survival (RFS) with adjuvant therapy for stage III/IV resected melanoma. For the case study, the MCM NMA was conducted by: (1) fitting MCMs to each trial included within the network of evidence; and (2) incorporating the parameters of the MCMs into a multivariate NMA. Outputs included relative effect estimates for the MCM NMA as well as absolute estimates of survival (RFS), modeled within the Bayesian multivariate NMA, by incorporating absolute baseline effects of the reference treatment. The case study was intended for illustrative purposes of the MCM NMA methodology and is not meant for clinical interpretation. The case study demonstrated the feasibility of conducting an MCM NMA and highlighted key issues and considerations when conducting such analyses, including plausibility of cure, maturity of data, process for model selection, and the presentation and interpretation of results. MCM NMA provides a method of comparative survival that acknowledges the benefit newer treatments may confer on a subset of patients, resulting in long-term survival and reflection of this survival in extrapolation. In the future, this method may provide an additional metric to compare treatments that is of value to patients.