Incidence and Costs of Clinically Significant Events with Systemic Therapy in Patients with Unresectable Hepatocellular Carcinoma: A Retrospective Cohort Study.

INTRODUCTION: Systemic therapies have been associated with clinically significant events (CSEs) in patients with unresectable hepatocellular carcinoma (uHCC). We evaluated the incidence of CSEs (bleeding, clotting, encephalopathy, and portal hypertension), and their impact on healthcare resource utilization (HCRU) and costs, in patients with uHCC treated with first-line (1L) atezolizumab plus bevacizumab (A + B), lenvatinib (LEN), or sorafenib (SOR) in the USA. METHODS: A retrospective cohort study was performed using medical/pharmacy claims from Optum® Clinformatics® Data Mart. Patients diagnosed with HCC who initiated 1L A + B between June 01, 2020 and December 31, 2020 or LEN/SOR between January 01, 2016 and May 31, 2020 were included. Outcomes included incidence rates of CSEs, HCRU, and costs. Subgroup analysis was performed in patients with no CSEs or ≥ 1 CSE. RESULTS: In total, 1379 patients were selected (A + B, n = 271; LEN, n = 217; SOR, n = 891). Clotting (incidence rate per 100 patient-years [PY] 94.9) and bleeding (88.1 per 100 PY) were the most common CSEs in the A + B cohort. The most common CSEs in the LEN cohort were clotting (78.6 per 100 PY) and encephalopathy (66.3 per 100 PY). Encephalopathy (73.0 per 100 PY) and portal hypertension (72.3 per 100 PY) were the most common CSEs in the SOR cohort. Mean total all-cause healthcare costs per patient per month (PPPM) were $32,742, $35,623, and $29,173 in the A + B, LEN, and SOR cohorts, respectively. Mean total all-cause healthcare costs PPPM were higher in patients who had ≥ 1 CSE versus those who did not (A + B $34,304 versus $30,889; LEN $39,591 versus $30,621; SOR $31,022 versus $27,003). CONCLUSION: Despite improved efficacy of 1L systemic therapies, CSEs remain a concern for patients with uHCC, as well as an economic burden to the healthcare system. Newer treatments that reduce the risk of CSEs, while improving long-term survival in patients with uHCC, are warranted.

Certain treatments for liver cancer can cause serious side effects, including bleeding, blood clots, brain injury (encephalopathy), or increased blood flow to the liver (portal hypertension). We used an insurance database to find out how often these events, known as clinically significant events, occurred in people with liver cancer who were given treatments that target the immune system (immunotherapy) or specific proteins involved in cancer growth and survival (targeted therapy). The study included 1379 patients treated with atezolizumab (immunotherapy) plus bevacizumab (targeted therapy), or lenvatinib or sorafenib alone (both targeted therapies), as their first treatment. Clotting and bleeding were the most common clinically significant events in patients treated with atezolizumab plus bevacizumab, whereas clotting and encephalopathy were the most common clinically significant events with lenvatinib, and encephalopathy and portal hypertension were the most common clinically significant events with sorafenib. On average, for every 100 patients treated for 1 year, there were more than 50 of each of these events. Average healthcare costs per patient per month ranged from around $29,000 to around $36,000 in the three different treatment groups, and were higher in people who had at least one clinically significant event. These results suggest that clinically significant events are common in people with liver cancer who are given various types of treatment. As well as raising concerns for patient safety, these events result in higher costs to healthcare systems. Therefore, newer treatments that are less likely to cause clinically significant events, while improving survival in patients with liver cancer, are needed.

Real-World Analysis of Treatment Patterns, Healthcare Utilization, Costs, and Mortality Among People with Biliary Tract Cancers in the USA.

INTRODUCTION: People with advanced biliary tract cancers (BTCs) have a 5-year survival of approximately 2% in the USA. Most cases are inoperable or require systemic treatment following surgery. This study adds to current literature by describing treatment patterns, healthcare resource utilization (HCRU), costs, and mortality among people with BTCs. METHODS: Adults diagnosed with BTCs were identified in the Merative MarketScan administrative claims databases from 1 January 2016 to 30 June 2020. Descriptive analysis was used to measure treatment patterns (i.e., regimen types, therapy duration) during three lines of therapy (LOT). All-cause and disease-related HCRU and costs were measured per-patient-per-month (PPPM) during the entire follow-up and in each LOT. Mortality was reported among the subset linked to the National Death Index (NDI). RESULTS: There were 2648 eligible people with BTCs [mean age 64.0 (standard deviation [SD] 12.4) years, 51.5% female, average follow-up 11.9 (SD 11.1) months]. Treatment was received by 56.3% (n = 1490), and 20.9% (n = 5534) and 7.1% (n = 187) moved on to a second and third LOT, respectively. The average treatment duration decreased across LOTs, from 3.8 (SD 3.1) months in LOT1 to 2.6 (SD 2.4) months in LOT3. Gemcitabine + cisplatin was the most common regimen in LOT1 (44.6%). Total all-cause mean healthcare costs PPPM increased after LOT1 (mean $21,517, $29,721, and $28,557, for LOT1, LOT2, and LOT3, respectively) and the majority (71.2%) were related to BTCs. Of people with BTCs linked to the NDI (n = 2168), 66.1% died and average time to death was 11.3 (SD 11.2) months. CONCLUSIONS: These findings, showing a high rate of mortality, a decrease in treatment duration, and an increase in costs as people progress after LOT1, add recent data to current literature highlighting the unmet need for more effective treatment options for people with BTCs.