Kishan Patel, MD, Yale School of Medicine, New Haven, CT, discusses results from cost-effectiveness study examining atezolizumab plus bevacizumab in advanced hepatocellular carcinoma, finding that this treatment is not cost-effective under current pricing.

This study was presented at the virtual 2021 ASCO Annual Meeting.

Transcript:

Hi, everybody. I'm Kishan Patel. I presented a study titled "The Cost Effectiveness of Atezolizumab and Bevacizumab in Advanced Hepatocellular Carcinoma" at ASCO 2021. I was a medical student at Yale at the time of writing of that abstract. I'm currently an internal medicine resident at Brigham and Women's Hospital in Boston.

A bit of background about the study. This was a cost-effectiveness study based on the IMbrave150 trial that was a phase III study that was published that compared a combination regimen of atezolizumab and bevacizumab versus the standard of care in unresectable HCC, which is sorafenib.

Just to break that down, atezolizumab is a immunotherapy agent. It's a PD-1 inhibitor. Bevacizumab is a VEGF, a vascular endothelial growth factor inhibitor, and sorafenib is a multikinase inhibitor. Based on the SHARP trial, sorafenib has been the standard of care in this particular patient population.

The IMbrave trial basically showed that combination therapy with atezolizumab and bevacizumab significantly prolonged overall survival in this patient population. After a month of follow-up, the OS rates in the combination group was about 67% compared to about 55% in the sorafenib group.

That was exciting news for HCC patients and HCC clinicians. Atezolizumab/bevacizumab was quickly approved by the FDA and now is listed as a Category 1 recommendation by the National Comprehensive Cancer Network.

Despite the survival benefit seen in the IMbrave trial, it's unclear whether the combination therapy of atezo/bev is actually cost-effective compared to sorafenib. Both of those agents, atezolizumab and bevacizumab, are costly drugs.

Atezolizumab costs about $9,400 per infusion. Bev costs about $8,400 per infusion. With treatment administered every 3 weeks, the estimated total cost of therapy over, for example, the 7 months of median exposure to therapy in the trial exceeds $180,000.

We hypothesized in the study that use of this combination therapy in this particular patient population would not be cost-effective compared to sorafenib. The way that we were assessing this was using something called partition survival analysis. It's a type of cost-effectiveness model that extrapolates survival, both via the progression-free survival and overall survival curves from the actual study itself.

Survival, as I mentioned, was based on the trial. We got utility measurements from the literature and then cost of treatment, adverse events, terminal care, things like that were determined mainly from Medicare fee schedules but also from prior literature as well.

What we calculated was something called the incremental cost-effectiveness ratio, or the ICER, of atezo/bev compared to sorafenib. That has units of dollars per QALY and basically represents the amount of money that's required to extend the life of a single patient by a single QALY if you use atezo/bev as opposed to sorafenib.

We were comparing that to a willingness-to-pay threshold of $150,000 per QALY, which is a fairly generous threshold that is often used in the cancer literature.

In this particular study, we showed that over a lifetime horizon -- meaning from the start of therapy all the way until death -- atezo/bev was associated with an incremental cost of about $100,000 as well as an incremental effectiveness about 0.42 quality-adjusted life years compared to sorafenib.

The ICER of the combination regimen was over $240,000 per QALY. Since that was above our willingness-to-pay threshold, we concluded that combination therapy with both agents was not cost-effective.

Our model also showed that the price of atezolizumab would need to be decreased by 40%, the price of bev by 47%, or the price of both by about 21% in order for that combination therapy to be cost-effective.

Then we did a number of sensitivity analyses as well. Across all the sensitivity analyses, atezo/bev was not found to be cost-effective. The only situation where it could be cost-effective was if we had the most generous hazard ratios at the lower end of the 95% confidence interval that was reported in the trial.

The conclusions were that use of this combination therapy is not cost-effective compared to sorafenib under current pricing. This is adding to a history of literature, I guess, recently looking at cost-effectiveness of cancer agents.

The cost of cancer drugs has really risen dramatically over the last 50 years unlike other countries that have regulatory bodies that can help negotiate drug pricing. We don't have that kind of system in the United States.

We're finding that a lot of the drugs that are approved by the FDA are approved with high prices that aren't warranted, given the clinical effectiveness of the drugs. I think it reinforces a need for different price systems in the United States, like value-based pricing, that could more closely align the utility of these drugs with their cost.

Thanks for listening. I appreciate it.