Treatment Patterns for Hepatocellular Carcinoma

Christopher R. Manz, MD, MSHP, Dana-Farber Cancer Institute, Boston, Massachusetts, discusses the retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER)–Medicare data to examine population-level treatment patterns for hepatocellular carcinoma since the approvals of new therapies between 2017 and 2022.

Through this study, Dr Manz concluded, “As anticipated, we found that local therapy treatment patterns were largely stable, but that there are significant changes in preferred first-line treatment.” He went on to highlight the importance of understanding, “how these treatment patterns have continued to evolve into 2022, 2023, and 2024 as we now have different care standards” as well as “the ways that people are treating patients as first-line treatment for HCC and ideally what are the additional treatments that patients receive after first-line treatment.”

Transcript:

Hi, I'm Chris Manz. I'm a medical oncologist at the Dana-Farber Cancer Institute. I'm going to talk about a study that we recently published about HCC treatment patterns.

In the United States, hepatocellular carcinoma, or HCC, is the sixth leading cause of cancer deaths. And it's expected to become the third leading cause of cancer deaths over the next 15 years. Historically, we've had very few treatment options for HCC, with only one FDA -approved drug. However, between 2017 and 2022, there were 9 FDA approvals for HCC. The purpose of this study was to describe changes in treatment patterns in recent years with the emergence of these new therapies.

In this study, we took SEER–Medicare registry and claims data that included patients with a diagnosis of HCC between 2014 and 2019 and their treatment claims through the end of 2020. This is the most recent data that's available for this registry. We looked at 3 sets of outcomes: we looked at whether they received what we call local therapies which are treatments like surgery or embolization like TACE [transarterial chemoembolization] or TARE [transarterial radioembolization]; we looked at receipt of systemic therapies which included all FDA-approved drugs during the study period; and we also looked at overall survival.

What we found in this study is that only about 60% of patients with HCC receive any treatment in their first year after their diagnosis. About 50% of patients receive a local therapy of some sort, and 15% of patients receive systemic therapy in that first year. And the numbers don't quite add up to 60% because some patients get both. However, about 40 % of patients don't receive any treatment at all for their cancers, and these numbers didn't really change over our study period from 2014 until 2019.

Of the patients that received local therapies, about 70% of patients received an embolization of some sort, whether TACE or TARE. Another 25% of patients received ablation and the remaining local therapies were used with lesser frequency. There's a very slight decrease over the study period in the percentages of patients receiving embolization or transplant, just a couple of percentage points, but otherwise there are no major changes in receipt of local therapies. However, there were changes in the receipt of systemic therapies over the study period.

For patients that were diagnosed with HCC in 2014, sorafenib was by far the first drug that they received as a systemic therapy. Every year thereafter, there was a steady decrease in patients who received sorafenib. So that patients that were diagnosed with HCC in 2019 were equally likely to get sorafenib or lenvatinib, and nivolumab was the third most common treatment that was administered as a first-line treatment for patients diagnosed with HCC in 2019. However, despite the fact that by 2020, there were a number of approved treatment options for HCC, only 20% of patients who started first-line treatment with a systemic therapy ever received a second-line of treatment.

When we looked at survival, we found that patients that received no treatment whatsoever had a median survival of only 2 months. For patients that received systemic therapies first, the median survival was about 12 months. And for patients that received a local therapy first, median survival was 24 months. Fortunately, we saw that the hazard of death, adjusting for a number of factors, decreased by about 20% over the study period. There's actually substantial improvement in survival for those patients receiving systemic therapy first, but actually worst survival for patients starting local therapy first when we look at 2019 compared to 2014.

There's a number of key points that I want to pull out of this study. As anticipated, we found that local therapy treatment patterns were largely stable, but that there are significant changes in preferred first-line treatment. By the end of the study period, lenvatinib was the favored first-line treatment. However, I'll point out that our current guidelines recommend first-line treatment with atezolizumab and bevacizumab or durvalumab and tremelimumab. And in this study, we don't really observe the use of those therapies because atezolizumab-bevacizumab was just approved in 2020, near the very end of our observation period. And durvalumab-tremelimumab wasn't approved until 2022.

The other thing I wanted to highlight is that 40% of patients never get treated at all. And of all patients, only 20% ever receive systemic therapy and of those, only 20% receive a second line of systemic therapy. So, there's a lot of work to be done to be able to extend the benefits of our existing treatment options to all patients with HCC. It's very encouraging to see that we're seeing an increase in overall survival, especially in that systemic therapy first group, but why is survival getting worse for the patients in the local therapy first group? It's probably not any change in the effectiveness of the local therapies themselves, rather it probably represents a shift in who is getting treated, where some healthier patients that otherwise would have been getting local therapy first might be getting systemic therapy first.

In terms of next steps, we really need to understand how these treatment patterns have continued to evolve into 2022, 2023, and 2024 as we now have different care standards and we need to understand what are the ways that people are treating patients as first-line treatment for HCC and ideally what are the additional treatments that patients receive after first-line treatment.

Source:

Iheanacho F, Tramontano AC, Abrams TA, et al. Changing Treatment patterns for hepatocellular carcinoma: A Surveillance, Epidemiology, and End Results–Medicare study. Cancer. Published online: November 12, 2024. doi:10.1002/cncr.35649