A recent study presented at the European Society for Medical Oncology (ESMO) Congress 2024 suggests that using biomarker-guided selection for first-line nivolumab treatment in patients with microsatellite stable (MSS)/proficient mismatch repair (pMMR) metastatic colorectal cancer (mCRC) could improve cost-effectiveness and treatment efficacy. The research, led by Benjamin Geisler, MD, MPH, indicates that identifying suitable patients based on biomarkers such as tumor mutational burden (TMB), target lesion reduction, and C-reactive protein levels may optimize the use of nivolumab in this patient population.
The study utilized data from the phase 2 randomized controlled trial METIMMOX-1 to develop a partitioned survival model. This model compared the cost-effectiveness of FLOX chemotherapy alone versus alternating FLOX with nivolumab, both with and without biomarker-selected subgroups. The analysis incorporated progression-free survival (PFS) and overall survival (OS), health-related quality of life assessments, and healthcare costs estimated in 2023 Euros, including second-line and end-of-life care.
Cost-Effectiveness Analysis
The incremental cost-effectiveness ratio (ICER) was calculated for all patients and subgroups, using cut-offs of at least 10% target lesion reduction, TMB greater than 8.0 mut/MB, and C-reactive protein less than 5.0 mg/L at the start of nivolumab treatment. All outcomes were discounted at 4% per year. Geisler noted that a Norwegian threshold of approximately €51,000 was used to determine cost-effectiveness.
Baseline characteristics included 76 patients, with 46.1% being women and a median age of 64.5 years. The cost per FLOX cycle was estimated at €427, while each nivolumab cycle cost €13,923. The mean cost of the last month of a patient’s life was €13,803, and next-generation sequencing cost €1439.
Impact of Biomarker-Guided Selection
Treating all patients with nivolumab resulted in 0.1175 quality-adjusted life years (QALYs) at an incremental cost exceeding €75,000, yielding an ICER of €638,798, which is not cost-effective. However, biomarker-guided selection significantly improved these outcomes. For patients with at least a 10% target lesion reduction, incremental costs decreased to €30,386, QALYs increased to 0.2112, and the ICER dropped to €143,850. Similar trends were observed in patients with C-reactive protein levels below 5.0 mg/L (ICER of €112,840) and those with TMB greater than 8.0 mut/MB (ICER of €45,451).
Study Limitations and Future Directions
Geisler acknowledged several limitations, including the post-hoc nature of the analysis, the lack of TMB data in the control group, and the dependence on Norwegian costs. He emphasized the need for a probabilistic sensitivity analysis to address the small sample size. Despite these limitations, the findings suggest that biomarker-guided selection for anti-PD-1 therapy may improve clinical effectiveness and lower costs in MSS/pMMR mCRC.
"Biomarker guided selection for anti-PD-1 compared to treating all metastatic MSS patients may improve its clinical effectiveness while lowering costs, making it potentially cost effective, at least in Norway," Geisler concluded. "In particular the value of a [TMB] strategy is promising, and prospective validation should strongly be considered."
