Manish Kohli, MD, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT, discussed an abstract he presented at the 2023 ASCO GU Cancers Symposium titled, “Cost-effectiveness analysis of seven treatment regimens in metastatic hormone-sensitive prostate cancer: A public payer perspective using network meta-analysis.”

This study found that Enzalutamide plus androgen deprivation therapy was the most cost-effective option with a willingness-to-pay threshold as high as $500,000 per quality-adjusted life year (QALY), while Abiraterone Acetate plus Prednisone plus androgen deprivation therapy was the most cost-effective option at a willingness-to-pay threshold of $150,000 per QALY. 

Transcript:

I am Manish Kohli. I am a Professor of Medicine at the Huntsman Cancer Institute and the University of Utah. I will be presenting and talking about an abstract and poster that was presented at the American Society of Clinical Oncology Genitourinary Symposium in February 2023. The title of the abstract is “Cost-Effectiveness Analysis of Seven Treatment Regimens in Metastatic Hormone-Sensitive Prostate Cancer Using Network Meta-Analyses.”

It is important to know that we have graduated since 2015 with androgen deprivation therapy treatments alone for metastatic hormone-sensitive prostate cancer to doublets and triplets in these last seven to eight years. We have a plethora of Phase III randomized clinical trials showing doublets being superior to androgen deprivation therapy, which was the standard for about 70, 80 years now.

The treatment doublets that we now have, which are standard of care for this disease at this state of progression include docetaxel with androgen deprivation therapy, abiraterone with prednisone and androgen deprivation therapy, apalutamide with androgen deprivation therapy, enzalutamide with androgen deprivation therapy, darolutamide with docetaxel and with and androgen deprivation therapy, enzalutamide with androgen deprivation therapy with the majority of the patients receiving docetaxel.

So the whole field has gotten extremely complicated in trying to decide how to give which patient which of these treatments, especially because we do not have a predictive biomarker for any of them. All of them are treatments which are rational and standard. All of them are better than androgen deprivation therapy. There are no clinical trials in this space which compare head-to-head these treatments. So in that context, we embarked on doing a cost-effectiveness analysis. In layman terms, trying to find out what's the bang for the buck in terms of the drug and the drug buying us both longevity of life and quality of life. That's the cost-effectiveness analysis that was presented on February 23 at ASCO GU Symposium.

For this what we used is a decision analytical model, which is pretty standard in these kinds of studies. The name of this model is called a Partitioned Survival Analysis. So this was developed to describe the treatment course of patients which are diagnosed with metastatic hormone-sensitive prostate cancer. The costs that we used was from a US public perspective from the Department of Veterans Affairs, which is also labeled as federal supply scheme costs. Since it's a single payer system, there is standardization of the costs that we could use to calculate our cost-effectiveness analysis. So our Partitioned Survival Analysis has got three states: A patient on treatment with any of these regimens is in a progression-free state or is in a progressive state of disease, in other words, the treatment is failing, or the patient is dead. Those are the three health states. What the Partitioned Survive Analysis does is that it derives the proportion of patients in each of these health states at each time points of the progression-free survival curves supplied by these published results, as well as the overall survival curves of these published results, and it does so on a monthly basis.

Now, that's important to know as to how many patients are in each of these different health states. Then we do the cost analysis for these patients. The costs in our analysis took into account the cost for buying the drug, the cost for managing the side effects and the toxicity of the drug while being administered, the cost for downstream when the patient progresses on this drug regimen, the treatments that are given in castrate-resistant state and the costs for quality of life and best supportive care thereof also.

The effectiveness, on the other hand, is measured by what again was pretty standard to do in these kinds of studies, the quality-adjusted life years. This is a metric that represents the degree to which a treatment extends the life of a person as well as improves the quality of life of the person. The way this is estimated in the model is the time spent by the patients in each of these health states that I was talking about (Is the patient progression-free while on treatment? Is the patient progressive or is the patient dead?) on a monthly cycle.

So it weights the time that each patient is in these three states, and then it calculates a utility score which ranges from zero, which is that the patient is dead, to one, which is perfect health. So these utility scores for each treatment strategy was calculated from published literature. Among these treatment strategies, you can easily recognize that the progression-free survival utility values will be highest for patients who are receiving the treatment and are not progressing, are responding to it. Second will be lower than that will be the utility scores that will be given to a patient who's progressing because they're having some side effects as disease progresses. Of course, like I said, it's zero for death.

So as an example, the utility score for apalutamide with androgen deprivation therapy of a patient who is responding to treatment is about 0.8, by calculating it at the median progression-free survival curve of the published literature. While for androgen deprivation therapy, it is for the same patient, control arm is about 0.6. So we take these utilities and we calculate the quality-adjusted life years. Then we also have a sensitivity analysis that we do on the costs of the drugs to identify at which threshold a particular treatment is going to be more effective or the other. Does that change if the costs were to go up while the one treatment may have a higher cost and the other may have a lower cost, et cetera?

So when we put all these metrics together, we have a ratio that we calculate, and that ratio is the metric that we are after. That ratio is called the incremental cost-effectiveness ratio. It is calculated by taking the total cost of a treatment, like I said, the cost of purchasing the drug, the cost of managing the toxicity, the cost of the treatments that are being given, so you take the cost off all of that, you subtract the cost for doing ADT alone, and then you divide it by the effectiveness of the treatment regimen minus the effectiveness of ADT alone. That's called the incremental cost-effective ratio. So we calculate the incremental cost-effective ratios of all of these drugs, and that's what helps us decide what is the most effective treatment and at what price are we delivering that particular treatment.

So what we found out was that the effectiveness of androgen deprivation therapy is about the ICER, or the incremental cost-effective ratio, is the reference that we take, which we use against the other treatments ... The effectiveness of androgen deprivation therapy in terms of quality-adjusted life years is about 3.25 using their VA FSS scheme costs, and the cost for that is about $32,000 over a 10-year lifespan. Similarly, the cost of abiraterone with prednisone and androgen deprivation therapy, the cost is higher than ADT alone as is expected, about $45,000, and the effectiveness is slightly higher at 3.83.

Then as another example, for apalutamide and androgen deprivation therapy, the cost goes up higher to $68,000, but the effectiveness also goes up higher, 4.16 quality of life years. Suddenly, when we start looking at these numbers, even though the cost of giving, the third example of apalutamide with androgen deprivation therapy is higher, it's buying us more effectiveness or quality of life adjusted years, and the incremental cost-effective ratio when we calculate it for all of these different drug regimens, we found that the apalutamide with the androgen deprivation therapy had the highest incremental cost-effective ratio in the sense that if a payer was ready to pay $70,000 approximately, it would be that much amount of money spent to buy one quality-adjusted life year. That sum for enzalutamide and androgen deprivation therapy was $1,017,000. So even though for enzalutamide, the effectiveness, quality-adjusted life year, was higher than for apalutamide, the cost for the drug decreased the incremental cost-effective ratio for this combination over apalutamide and androgen deprivation therapy alone.

So by doing these kinds of analysis, we are not compromising a standard of care, we are not compromising effectiveness; we are calculating “what's the best treatment given in terms of both cost, management of toxicity and survival data, and is there a lesser expensive regimen that buys us the same life, longevity and quality of life?” Doing this math, we found that apalutamide along with androgen deprivation therapy, out of all the different regimens, trumps all and dominates the incremental cost-effective ratio for all other treatment regimens at a willingness-to-pay set by the payer of $100,000.

If that willingness-to-pay goes up to $1,000,000, then suddenly we see a switch, with enzalutamide and androgen deprivation therapy having a higher incremental cost-effective ratio. So it boils down to: how much is the payer willing to pay to buy the most effective treatment? This was our analysis that we have done using the costs that are used in the VA federal supply scheme, the public payer system, and those are our conclusions from this particular analysis. We have to look at this only because we don't have a head-to-head comparison of all these treatment regimens, and we do not have validated predictive biomarkers telling us or guiding us which of this is better than the other.

Reference

Kohli M, Dougherty M, Cutshall Z, et al. Cost-effectiveness analysis of seven treatment regimens in metastatic hormone-sensitive prostate cancer (mHSPC): A public payer perspective using network meta-analysis. Presented at: the 2023 ASCO GU Cancers Symposium; February 16-18, 2023; San Francisco, CA, and virtual; Abstract 268.