ArticleFrontiers in pharmacology2025
Beyond efficacy parity: a novel cost-equilibrium framework for value assessment of competing third-line therapies in metastatic colorectal cancer.
Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Colorectal cancer remains a leading cause of global cancer mortality, with metastatic CRC (mCRC) requiring sequential therapies after first line treatment failure. While regorafenib and fruquintinib are guideline-endorsed third-line options, their comparative value remains unestablished due to absent head-to-head trials. This real-world study evaluates clinical outcomes, safety, and cost differentials to model value-equilibrium pricing. Methods: A retrospective cohort analysis included 25 mCRC patients (regorafenib: n = 5; fruquintinib: n = 20) treated at Sichuan Cancer Hospital (2021-2022) with follow-up through June 2023. Outcomes included real-world disease control rate (rwDCR), adverse events (CTCAE v4.03-graded), and daily treatment costs (medication, dose adjustments, adverse event management). A Monte Carlo simulation modeled cost equilibrium using Generalized Beta Distribution-derived adverse event variability. Results: Baseline characteristics were balanced (median age: 58-63; 60%-70% male). rwDCR showed no significant difference (20% vs 25%, p = 1.000). Regorafenib demonstrated higher grade 3-4 toxicities (60.0% vs 20.0%), including hepatotoxicity (40.0% vs 15.0%) and hand-foot skin reaction (20.0% vs 0%). Fruquintinib exhibited unique hypertension (10.0%) and proteinuria (20.0%). Regorafenib incurred 75% higher daily costs (¥455.53 vs ¥259.96, p = 0.001), primarily from medication expenses (¥439.82 vs ¥253.71, p = 0.014). Pharmacoeconomic modeling identified regorafenib's value-based pricing threshold at 47.35% of current costs (¥248.03/day; 95% CI: 247.98-248.09), revealing a 111% price-to-value mismatch. Conclusion: Fruquintinib demonstrates comparable efficacy with superior safety and cost-effectiveness in third-line mCRC. Regorafenib's pricing exceeds its clinical value by twofold, underscoring systemic misalignment between drug costs and therapeutic benefit. These findings advocate for value-driven pricing reforms integrating toxicity-related economic burdens and provide a replicable framework for indirect treatment comparisons in oncology. However, the small sample size reduced statistical power, potentially biasing the findings.
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