Real-World Analysis Highlights US Treatment Patterns for Frontline Atezolizumab/Bevacizumab in HCC

Amit G. Singal, MD, MS

Real-world data from a systemic review of treatment patterns in the United States showed that the majority of patients with hepatocellular carcinoma (HCC) administered atezolizumab (Tecentriq) and bevacizumab (Avastin) in the frontline setting discontinued treatment within 12 months, indicating the need for additional research on the effectiveness of this regimen for patients with high-risk disease, according to a poster presentation given at the 2023 International Liver Cancer Association Conference.¹

According to data collected from 825 patients at a median follow-up of 15.3 months, 72% of patients with HCC discontinued atezolizumab plus bevacizumab within 12 months of initiation. The Kaplan-Meier estimated median time to treatment discontinuation was 5.1 months; the calculated median time to discontinuation was 3.5 months (interquartile range [IQR], 2.1-6.3).

“Using a large-scale real-world database, this study reflects contemporary routine clinical practice; however, claims data do not capture clinical parameters, endpoints, reasons for treatment discontinuation, or death,” lead study investigator Amit G. Singal, MD, MS, a professor in the Department of Internal Medicine at UT Southwestern Medical Center in Dallas, Texas, and colleagues wrote in the poster.

Since the FDA approved atezolizumab plus bevacizumab for the treatment of patients with unresectable or metastatic HCC who have not received prior systemic therapy in May 2020, the combination has been a standard of care in the first-line setting for this patient population.^1,2 However, additional real-world data are needed to further detail the use of this combination in clinical practice and to examine subsequent therapies for this patient population.¹

This real-world analysis included patients with HCC at least 18 years of age treated with frontline atezolizumab plus bevacizumab. Patients must have had data available to investigators on their treatment, including from pre- and post-index date. Patients could not have had any other primary cancers or any systemic HCC treatment prior to atezolizumab plus bevacizumab.

The IQVIA Open-Source Medical and Pharmacy administrative claims database was utilized to select patients, and all variables were analyzed using appropriate statistical methods.

The goals of the study were to evaluate the proportion of patients who discontinued treatment of atezolizumab plus bevacizumab, determine the proportion of patients who switched to other systemic therapies following treatment, the time to discontinuation, and the time to next treatment.

Patients had a median age of 67 years, and 80% of patients were male. Regarding geographical region in the United States, 39% of patients were from the South, 28% were from the West, 20% were from the Midwest, 13% were from the Northeast, and location was unknown for less than 1% of patients. Notably, 57%, 39%, and 2% of patients had Commercial, Medicare, and Medicaid, respectively. Moreover, 4% of patients had hepatitis B, 20% had hepatitis C, and 5% reported alcohol abuse.

Liver-related comorbidities included cirrhosis (51%), ascites (25%), portal hypertension (18%), esophageal varices (18%), encephalopathy (9%), and gastrointestinal hemorrhage (2%). Twenty-two percent of patients had metastases. Other comorbidities included hypertension (46%), diabetes (30%), heart failure (4%), chronic kidney disease (4%), myocardial infraction (1%), and cerebral hemorrhage (1%). The mean Charlson Comorbidity Index was 5 (standard deviation, 3).

Prior treatments included analgesics (60%), antihypertensives (56%), diuretics (28%), antithrombotic agents (21%), systemic corticosteroids (16%), lactulose (9%), and rifaximin (4%).

Overall, 19% of patients received subsequent systemic therapies; targeted therapies were the most common subsequent option (13%), along with immunotherapy (5%). Additionally, lenvatinib (Lenvima), cabozantinib (Cabometyx), and nivolumab (Opdivo) were the most common subsequent agents at 6%, 4%, and 4%, respectively.

Among patients who went on to receive subsequent treatment options following treatment with atezolizumab and bevacizumab (n = 159), baseline demographics were similar to patients who did not receive subsequent treatment. non-switchers, although more non-switchers were at least 65 years of age, had a shorter median follow-up, and had fewer metastases than switchers.

In patients with 12 or more months of follow-up (n = 548), 4% of patients received a third subsequent treatment, and 1% received a fourth subsequent treatment. Notably, locoregional therapies were given to 2% of patients in the post-index period, and 18% of patients more than 1-month post-index had diagnostic esophagogastroduodenoscopy.

“Further research is needed to provide insight into the effectiveness of atezolizumab and bevacizumab in those at high risk with advanced disease,” study authors concluded.

References

1. Singal AG, Özgürdal K, Fan X, et al. Real-world systemic treatment patterns in U.S. patients with hepatocellular carcinoma: 2020–2022. Presented at: 2023 International Liver Cancer Association Conference; September 7-9, 2023; Amsterdam, Netherlands. Abstract P-93.
2. FDA approves atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma. News release. FDA. May 29, 2020. Accessed September 12, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-atezolizumab-plus-bevacizumab-unresectable-hepatocellular-carcinoma