Analysis Correlates Cost of Therapy With Improvement in Outcomes for Patients With HCC

Audrey Sternberg

According to an economic evaluation, the use of atezolizumab plus bevacizumab is not cost effective versus sorafenib for the treatment of hepatocellular carcinoma when considering life-years gained and willingness-to-pay thresholds.

The use of atezolizumab (Tecentriq) plus bevacizumab (Avastin) for the treatment of first-line unresectable or metastatic hepatocellular carcinoma (HCC) was considered not to be cost effective versus sorafenib (Nexavar) despite producing better outcomes, according to an economic evaluation published in JAMA Network Open.1

From a United States payer perspective, atezolizumab/bevacizumab was associated with an incremental cost of $156,210 per patient versus sorafenib, with the incremental cost-effectiveness ratio (ICER) never decreasing below the willingness-to-pay threshold of $150,000 per quality-adjusted life-year (QALY) in a 1-way sensitivity analysis.

“To date, atezolizumab plus bevacizumab is currently the first and only treatment superior to sorafenib, the standard of care for unresectable or metastatic HCC,” wrote the investigators, who were led by Xin Zhang, MD. “The findings of this economic evaluation suggest that from the perspective of US payers, atezolizumab plus bevacizumab is unlikely to be cost-effective under current drug pricing at willingness-to-pay thresholds of $100 000 to $150 000 per QALY compared with sorafenib for patients with unresectable or metastatic HCC who have not received systemic therapy.”

Results of the phase 3 IMbrave150 trial (NCT03434379) previously showed that the PD-L1/VEGF inhibitor combination was able to significantly improve survival in patients with unresectable or advanced HCC in the frontline setting versus sorafenib, supplanting it as the preferred therapy for this patient population.2 The regimen subsequently received FDA approval in May 2020.3

In the analysis performed from June through September 2020, with a 6-year investment period, hypothetical patients (n = 424) had an increase of 0.623 life years (1.840 vs 1.218) with atezolizumab plus bevacizumab versus sorafenib. QALYs were increased by 0.484 (1.412 vs 0.928, respectively).

The ICER per QALY was $322,500, ranging from $149,364 in the 5th percentile up to $683,744 in the 95th percentile. With willingness-to-pay thresholds of $100,000 and $150,000, the chances of combination being cost effective were 0.6% and 1.5%, respectively.

It was determined that to achieve cost-effectiveness within the proposed willingness-to-pay thresholds, the costs of atezolizumab and bevacizumab would need to be reduced by 37% and 47%, respectively.

Of note, the investigators stated in their discussion that the “finding does not suggest opposition to the use of atezolizumab plus bevacizumab for patients with late-stage HCC but rather suggests that policy makers spend more resources on more cost-effective interventions,” citing increased HCC screenings for patients with cirrhosis. They believe these findings support strategies to maximize health gains in patients.

Limitations of the study include the unknown long-term effects of atezolizumab and bevacizumab on this patient population, as the therapy has not been available for long enough to assess any plateaus appearing on survival curves. Additionally, the model relied solely on results of the IMbrave150 trial, as no other studies comparing the designated experimental and comparator regimens were available.

The investigators also noted that lenvatinib (Lenvima), another therapy approved to treat HCC in the frontline setting, was not evaluated in this analysis. However, with its similar effectiveness and lower cost compared with sorafenib, it can be assumed that atezolizumab and bevacizumab would not be cost effective compared with lenvatinib.

References

1. Zhang X, Wang J, Shi J, Jia X, Dang S, Wang W. Cost-effectiveness of Atezolizumab Plus Bevacizumab vs Sorafenib for Patients With Unresectable or Metastatic Hepatocellular Carcinoma. JAMA Netw Open. 2021;4(4):e214846. doi:10.1001/jamanetworkopen.2021.4846

2. Finn RS, Qin S, Ikeda M, et al. IMbrave150 Investigators. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894-1905. doi:10.1056/NEJMoa1915745

3. FDA approves atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma. FDA. May 29, 2020. Accessed May 12, 2021. https://bit.ly/3o7xMEg