November 08, 2017
2 min read

Regorafenib not cost-effective as second-line therapy for hepatocellular carcinoma

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Neehar D. Parikh

Although clinically effective, the use of regorafenib as second-line therapy for hepatocellular carcinoma did not appear cost-effective, according to study results.

Regorafenib (Stivarga, Bayer) demonstrated an incremental cost-effectiveness ratio (ICER) of $224,362 per quality-adjusted life-year (QALY) compared with best supportive care.

“A significant reduction in the cost of regorafenib, to better reflect its overall clinical value, or better selection of patients in whom survival benefit can be maximized would greatly impact the cost-effectiveness of regorafenib,” Neehar D. Parikh, MD, MS, gastroenterologist at University of Michigan, and colleagues wrote.

Results of the RESORCE trial — which compared the efficacy of regorafenib with best supportive care among patients who progressed on sorafenib (Nexavar, Bayer) — showed regorafenib conferred longer median survival over placebo (10.6 months vs. 7.8 months; P < .001).

However, other research showed regorafenib was not a cost-effective third-line agent compared with placebo among patients with metastatic colorectal cancer, with an ICER of $900,000 per QALY.

Because regorafenib is newly indicated for HCC treatment, Parikh and colleagues sought to examine the cost-effectiveness of regorafenib as second-line treatment for advanced disease.

Researchers constructed a Markov simulation model that estimated QALYs and the ICER of regorafenib therapy compared with best supportive care among patients with unresectable HCC and Child-Pugh A cirrhosis.

Model inputs included efficacy and adverse events associated with regorafenib therapy based on published clinical trial data and literature review. Researchers calculated rates of HCC progression to match median OS, median PFS and median time-to-progression observed in the RESORCE trial.

PFS and OS rates in the model matched results of the RESORCE trial for both arms.

In the base case, regorafenib yielded an increase of 0.18 QALYs — or 65 quality-adjusted days — at a cost of $47,112, compared with $7,408 for best supportive care. This equated to an ICER of $224,362 compared with best supportive care, which researchers deemed was not cost effective.

Researchers also performed one-way sensitivity analyses on all model parameters, various Monte-Carlo simulation parameters and cost threshold analyses.

In these analyses, no scenarios showed regorafenib was cost-effective. The ICER for regorafenib remained above $140,000 per QALY in every one-way sensitivity analysis. Monte-Carlo simulation showed an ICER over $150,000 compared with best supportive care. Ninety-nine percent of simulations showed ICERs that exceeded $100,00, suggesting regorafenib therapy was unlikely to be cost-effective.

Cost-threshold analysis showed regorafenib would have to be priced at or below $67 per pill — compared with the standard $165 — to be cost-effective at an ICER of $100,000.


It remains unclear how much a 50% chance for an OS increase of less than 3 months is worth, especially when that extra time may come with additional physical costs, such as from drug-induced toxicities, Harold O. Douglass, Jr., MD, FACS, former chief of upper gastrointestinal surgery in the department of surgical oncology at Roswell Park Cancer Institute, wrote in an accompanying editorial.

“Most patients will suffer at least one minor drug-related adverse event and only one-half of those who are treated will derive any degree of benefit,” Douglass Jr. wrote. “For some, drug toxicity may cause survival to be shorter than if they had received no treatment at all.

“These are important ethical questions to which the oncologic community has given insufficient attention,” he added. – by Melinda Stevens

Disclosures: Parikh reports personal fees and nonfinancial support from Bayer and Eisai outside of the study. Please see the full study for a list of all other authors’ relevant financial disclosures. Douglass reports no relevant financial disclosures.