Real-World Study Shows Snapshot of a Survival Gap With Existing Therapies for Patients With HCC

Michael A. Morse, MD

Michael A. Morse, MD

In the community practice setting, patients with hepatocellular carcinoma (HCC) who receive systemic therapy have a poor prognosis, which reveals an unmet need for more effective treatment options, according to a real-world retrospective observational study. The study aimed to show how treatment patterns related to the overall survival (OS) of patients with HCC throughout the United States (U.S.).

The investigators of this study observed data from the Flatiron Health de-identified electronic health record—derived database, which showed a median OS of 16.6 months in 2134 patients across 5 subgroups, which included patients treated with either transplant, resection/stereotactic body radiation therapy (SBRT)/radiofrequency ablation (RFS), transarterial chemoembolization (TACE)/trans-arterial radioembolization (TARE)/transarterial embolization (TAE), a tyrosine kinase inhibitor (TKI), or a cancer immunotherapy (CIT). Treatment with a TKI had the lowest OS benefit at 5.0 months, and transplantation had the highest benefit at 71.5 months.

Several factors may contribute to the gap in OS, including doctors' notes at the beginning of care and the use of older agents when newer and more effective drugs have become available, said study lead, Michael A. Morse, MD. Additionally, it may not be pragmatic for community oncologists to follow the treatment standards born from clinical trials because average patients with HCC do not have the same outcomes as patients who undergo treatment in the clinical trial setting.

In an interview withTargeted Oncology, Morse, a professor of Medicine and professor of the Department of Surgery at Duke University, shared the unique findings from the retrospective observational real-world study of treatment patterns and survival in patients with HCC in the United States.

TARGETED ONCOLOGY: Can you provide background on your retrospective observational study of real-world data in HCC?

Morse: We wanted to obtain real-world data from community health records, and it turns out that Flatiron has access to large amounts of patient information, and we knew that within it, there would be patients with liver cancer. We wanted to get a snapshot of what the first patient treatment is for people with HCC. It's descriptive.

When people look at the poster, they looked at the survival curves and tried to compare them, and you can't. Arguably, there should be separate figures for each type of treatment because the participants are not in the same patient population. Patients who get TACE are not the same as patients who get systemic therapy as their first-line option because they can have different prognoses.

TARGETED ONCOLOGY: What was the goal of your observational study of the Flatiron Health database?

Morse: The objective of our study was to describe the first-line treatment distribution for real-world patients and then describe the OS of those patients, but not compare it by therapy.

TARGETED ONCOLOGY: What was interesting about the results of this study?

Morse: We laid out the demographics of people in this database. One important finding that was not a part of our conclusion was that physicians are not reporting a lot of information about their patients' stage of disease and liver function. It is not easy to find that information in the electronic health records, which led us to believe that it may not be a part of standard clinical practice. Since knowing the stage of a patient guides treatment, I think it's important that physicians consider that information.

The second thing we found was the survival of people who can undergo resections. For that curve, the median survival was about 5 years. This shows that there are subgroups of patients who should get aggressive therapy. If there was any nihilism out there about the longer-term benefit of operating on patients with HCC, the answer is that some patients do benefit from it.

The confidence intervals are quite large in this study, particularly for survival after resection and even RFA, TACE, and SBRT. That tells us that there is a lot of patient selection that is critical in maximizing the benefit of these therapies and that the benefit of therapy has a wide range. This sort of complicates thinking of clinical trials in these groups when you are trying to decide what the baseline survival is going to be for someone who is a resection candidate, for example, and many things have to be taken into account in these clinical trial populations.

On the other end of the spectrum, we have to look at clinical trial results for TKI monotherapy. The REFLECT trial, for example, has a 14-month median survival for lenvatinib; we're not seeing anything close to that in that study. TKI monotherapy is the first therapy for patients with HCC. The average person is not getting the benefit that we see in clinical trials. That doesn't mean they're not getting benefit compared to what would've happened if they didn't get therapy at all, but again, it indicates how important patient selection is. It also indicates that we need to be more aggressive about managing toxicities so that patients can remain on therapy. Lastly, even though didn't [highlight the relationship between toxicities and OS], they surely do affect OS. This study shows that many people aren't getting other therapies, and that's why the survival appears to be limited for TKI monotherapy.

TARGETED ONCOLOGY: What is the key message community oncologists should take away from this real-world research?

Morse: We need more effective therapies because we have a big gap between patients who can only get systemic therapy and patients who are eligible for local/regional therapy. This study is a snapshot that shows us real-world data can be used to start asking some questions about how to treat HCC, and we're indirectly inferring that there is a poor prognosis for patients with advanced disease. The survival that we're seeing in the TKI patients suggests that we can do better by applying other therapies and getting to people sooner. We also know that better systemic therapies are on the horizon. I think bevacizumab (Avastin) plus atezolizumab (Tecentriq), for example, may become the standard. We know that it was more effective than sorafenib. Based on this, we can say that we know that TKI monotherapy has a limited benefit, but we have other options that can enhance the benefit.