Atezolizumab Plus Bevacizumab Is Cost-Effective for Advanced HCC When Utilizing Biosimilars

J Clin Pathways. 2021;7(8):10-11.

With great interest, we viewed the recent video, “Atezolizumab Plus Bevacizumab Unlikely Cost-Effective for Advanced HCC,” created by Kishan Patel, MD, to describe the findings of his abstract that was accepted for publication at ASCO 2021.^1,2 In his message and abstract, the author argues that despite survival benefit seen in IMbrave150 the combination of atezolizumab + bevacizumab is not cost-effective when compared with sorafenib under current pricing.³ We disagree with these findings, on several points.

To support this conclusion, it is important to understand more about the cost calculations. The authors mention using ‘literature and Medicare fee schedules,’ but we do not know if they used the typical Centers for Medicare & Medicaid Services Average Sales Price (ASP) + 6% for intravenous agents and wholesale acquisition cost (WAC) for oral agents.^4,5 It appears they may have included direct costs related to adverse events and terminal care, but additional information was not provided to enable us to reproduce the calculation. It is not clear if costs for chair time, premedications, or other supportive care agents were included.

The authors suggest if the price of atezolizumab were reduced by 40% (to $5,700 per dose) or the price of bevacizumab were reduced by 47% (to $4,400 per dose), then the combination of atezolizumab + bevacizumab would be cost-effective when compared with sorafenib. The authors did not explore the incorporation of biosimilar bevacizumab into their calculations. The US Oncology Network adopted the utilization of biosimilar agents in 2020, shifting utilization from innovators to provide equivalent efficacy at a substantially lower Medicare allowable, saving money for the patient, the payer, and the practice.⁶ Using the least expensive biosimilar bevacizumab achieves the price suggested by the authors necessary to achieve cost-effectiveness. Based on the July 2021 Medicare allowable reimbursement (ASP + 6%) for biosimilar bevacizumab, the insurer responsibility is $4293 per dose (assuming a 20% patient responsibility).

Furthermore, we disagree with the annual cost used for sorafenib tosylate. Using July 2021 WAC, the calculation for 2 tablets twice daily (4 tablets daily) for 365 days exceeds the total cost used by the authors in their base-case model. Although the authors were using 2020 WAC, it is unlikely that the cost of sorafenib increased 15% over the last calendar year. By our calculation, the median extended WAC has increased 3.8%.

We have updated the cost-effectiveness analysis using the identical quality-adjusted life-year (QALY) information as Patel and colleagues but replaced the cost information with the ASP + 6% or WAC for 1 year of therapy. Although there may be other factors included in the total cost, we streamlined to Medicare allowable only, to show the impact biosimilar adoption can have on therapy overall. We determined the incremental cost-effectiveness ratio (ICER) to be $2,705. Incorporating biosimilar bevacizumab and using the current WAC for sorafenib results in the cost-effectiveness of an atezolizumab + bevacizumab combination for treatment of unresectable hepatocellular carcinoma.

It would be highly unlikely that payers would have included atezolizumab + bevacizumab as an option for first-line treatment and beyond for hepatocellular carcinoma if the combination were indeed not cost-effective. The current versions of Cigna Oncology Clinical Pathways, AIM Cancer Treatment Pathways, and UnitedHealthcare (UHC) Cancer Therapy Pathways include atezolizumab + bevacizumab as an on-pathway option, with UHC giving preference to the biosimilar version of bevacizumab.^7-9

In summary, we respectfully submit the calculation of ICER and highlight the impact biosimilar adoption can have on the cost-effectiveness of emerging therapies (Table). Incorporation of biosimilar bevacizumab enables the combination to beat the established willingness-to-pay threshold of $50,000/QALY, $100,000/QALY, and $150,000/QALY.

References

1. Patel K, Stein S, Luther J, et al. Cost-effectiveness of atezolizumab and bevacizumab in advanced hepatocellular carcinoma. Presented at: the 2021 ASCO Annual Meeting; June 4-8, 2021; virtual. Abstract e18829. https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.e18829

2. Patel K. Atezolizumab plus bevacizumab unlikely cost-effective for advanced HCC. J Clin Pathways. Published July 1, 2021. Accessed October 7, 2021. https://www.hmpgloballearningnetwork.com/site/jcp/videos/atezolizumab-plus-bevacizumab-unlikely-cost-effective-advanced-hcc

3. Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus Bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894-1905. doi: 10.1056/NEJMoa1915745

4. Centers for Medicare & Medicaid Services. July 2021 ASP pricing file. Updated September 9, 2021. Accessed October 7, 2021. https://www.cms.gov/medicare/medicare-part-b-drug-average-sales-price/2021-asp-drug-pricing-files

5. IBM. IBM Micromedex Web applications process. Published 2021. Accessed October 7, 2021. https://www.micromedexsolutions.com/home/dispatch

6. US Food and Drug Administration. Biosimilar development, review and approval. Updated October 20, 2017. Accessed October 7, 2021. https://www.fda.gov/drugs/biosimilars/biosimilar-development-review-and-approval

7. Cigna Oncology Clinical Pathways. Accessed October 13, 2021. https://static.cigna.com/assets/chcp/resourceLibrary/medicalResourcesList/medicalcommitment2Quality/commit2QualityCignaOncologyPathways.html

8. AIM Specialty Health. Hepatocellular carcinoma pathways. Updated April 20, 2021. Accessed October 7, 2021. https://aimproviders.com/wp-content/uploads/2021/06/Hepatocellular.pdf

9. UnitedHealthcare Services. UnitedHealthcare can-
cer therapy pathways program. Accessed October 7, 2021. https://www.uhcprovider.com/content/dam/provider/docs/public/prior-auth/
oncology/ctpp/Cancer-Therapy-Pathways-Program-Regimens.pdf

Author Information

Authors: Aimee Ginsburg, PharmD, BCPS¹; Leslie Busby, MD²; Kaci Dominguez, PharmD¹; Josh Howell, PharmD, BCOP¹

Affiliations: ¹McKesson Specialty Health, The Woodlands, TX; ²Rocky Mountain Cancer Centers, Boulder, CO/The US Oncology Network