(334) Nivolumab plus Ipilimumab as a First-line Treatment for MSI-H/dMMR Metastatic Colorectal Cancer: a Cost-per-Outcome Analysis

Background: : In CheckMate-8HW (CM-8HW), centrally confirmed microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC) patients treated with nivolumab (NIVO)+ipilimumab (IPI) showed significantly longer progression-free survival (PFS) vs chemotherapy (chemo) (HR first-line NIVO+IPI vs chemo: 0.21 [95%CI 0.14-0.32]) or nivolumab monotherapy (HR all-lines NIVO+IPI vs NIVO: 0.62 [95%CI 0.48-0.81]). In KeyNote177 (KN-177), pembrolizumab (PEMBRO) improved PFS vs chemo in locally confirmed first-line MSI-H/dMMR mCRC patients (HR PEMBRO vs chemo: 0.60 [95%CI 0.45-0.80]). However, first-line comparisons between NIVO+IPI and PEMBRO are lacking, highlighting the need for clinical and economic comparisons of first-line mCRC treatments to inform healthcare decision-making.

Objective: : To compare the total costs, PFS, and the costs per PFS month gained of NIVO+IPI vs chemo, PEMBRO vs chemo and NIVO+IPI vs PEMBRO in first-line MSI-H/dMMR mCRC patients.

Methods: : A three-state semi-Markov model comprising progression-free, progressed, and dead health states was developed. Results were presented for 24-, 36- (trial) and 60-month (model) time horizons. Effectiveness data from locally assessed MSI-H/dMMR mCRC patients for NIVO+IPI, chemo, and PEMBRO was sourced from CM-8HW (DBL Sep2024), CM-142 and KN-177. An indirect treatment comparison (ITC) was performed between NIVO+IPI and PEMBRO using four methods: time-varying parametric analysis, anchored matching adjusted indirect comparisons (MAIC), unanchored MAICs, and fractional polynomial network meta-analyses. Treatment acquisition, administration, disease management, and adverse event costs were sourced from U.S. databases and reported in 2025 USD.

Results: : At 24-, 36- and 60-months, NIVO+IPI demonstrated superior clinical outcomes vs chemo and PEMBRO in first-line MSI-H/dMMR mCRC. Although upfront drug acquisition costs were higher for NIVO+IPI, disease management costs were higher for PEMBRO and increased over time. NIVO+IPI showed lower costs per PFS gained when compared to chemo at 24-,36- and 60-months ($35,475; $18,570; $8,743) vs PEMBRO ($68,253; $31,253; $14,286). Compared to PEMBRO, the costs per PFS month gained of NIVO+IPI were $23,526, $12,826 and $5,939. Despite higher acquisition costs, NIVO+IPI lies on the cost-effectiveness efficiency frontier, offering greater value than PEMBRO.

Conclusions: : Given its significant PFS benefits, and lower costs per PFS month gained vs chemo, NIVO+IPI provides superior value compared to PEMBRO as a first-line treatment for MSI-H/dMMR mCRC patients.

Sponsorship:: Bristol Myers Squibb