ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Drugs Outcomes Research and Policies
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1606742
Beyond Efficacy Parity: A Novel Cost-Equilibrium Framework for Value Assessment of Competing Third-Line Therapies in Metastatic Colorectal Cancer
Provisionally accepted
- 1Department of Pharmacy, Sichuan Cancer Hospital, Chengdu, China
- 2Sichuan Cancer Hospital, Chengdu, Sichuan Province, China
- 3Faculty of Science and Technology University of Macau, Macau, China
- 4Second People’s Hospital of Yibin, Yibin, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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.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..
Keywords: fruquintinib, Regorafenib, cost, equilibrium, mathematical model
Received: 07 Apr 2025; Accepted: 30 Jul 2025.
Copyright: © 2025 Long, Wang, Luo and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jing Luo, Second People’s Hospital of Yibin, Yibin, 644000, China
Qian Jiang, Department of Pharmacy, Sichuan Cancer Hospital, Chengdu, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.