Complete response and long-term survival possible with locoregional therapy plus IO in patients with unresectable HCC
20 Nov 2024
byNatalia Reoutova
A cohort study conducted by researchers
from the University of Hong Kong (HKU) reports a complete response (CR) rate of
46.0 percent among patients with locally advanced, unresectable hepatocellular
carcinoma (HCC) who were treated with locoregional therapy (LRT) plus immunotherapy
(IO) and a 3-year overall survival (OS) rate of 75.5 percent among patients
with CR.
A previous study reported a CR rate of 42 percent among patients with locally advanced HCC treated with combined LRT plus IO (LRT-IO), however, data on predictors of CR and long-term survival without surgery and after discontinuation of IO were lacking. [Lancet Gastroenterol Hepatol 2023;8:169-178] “The objective of the present study was to assess the long-term clinical outcomes among patients with unresectable HCC who achieved CR after LRT-IO and were placed on a watch-and-wait protocol,” explained the researchers.
A total of 63 patients (median age, 69 years; male, 92.1 percent) with locally advanced, unresectable HCC (median tumour diameter, 10 cm; macrovascular invasion in 60.3 percent of patients) were treated with LRT (transarterial chemoembolization and/or stereotactic body radiotherapy) followed by at least one dose of IO (avelumab, nivolumab or pembrolizumab) at Queen Mary Hospital, Tuen Mun Hospital and University of Hong Kong–Shenzhen Hospital between January 2018 and December 2022. [JAMA Oncol 2024;doi:10.1001/jamaoncol.2024.4085]
At a median follow-up of 34.7 months, 46.0 percent of patients achieved CR, 28.6 percent achieved partial response, 9.5 percent had stable disease, and 15.9 percent experienced disease progression. Among patients with CR, 34.5 percent had Barcelona Clinic Liver Cancer stage A disease, while the rest had stage B or C disease. Patients who attained CR had significantly improved 3-year OS rates vs those who did not (75.5 vs 28.1 percent; 95 percent confidence interval [CI], 7.4–29.4; p<0.001). “Treatment response [hazard ratio, 5.10; 95 percent CI, 1.90–13.64; p=0.001] was the only independent factor associated with survival. Notably, there was no significant association between the duration of IO, type of LRT and grade ≥3 or higher immune-related adverse events [AEs] with CR,” reported the researchers.
The median time to CR was 5.4 months, while the median duration of CR was 25.7 months. Of patients with CR, 20.7 percent died before study completion due to HCC progression (6.9 percent), cardiac arrhythmia (6.9 percent), COVID-19 (3.4 percent), and cirrhosis (3.4 percent). At least one grade ≥3 treatment-related AE was experienced by 23.8 percent of patients, of which transient increases in alanine aminotransferase, aspartate aminotransferase or bilirubin levels (66.7 percent) were the most common. Immune-related AEs were reported in 12.7 percent of patients (hepatitis, 7.9 percent; dermatitis, 4.8 percent). Child-Pugh score deterioration of ≥2 was detected in 10.2 percent of patients at 3 months, 9.1 percent at 6 months and 6.2 percent at 12 months.
“The watch-and-wait strategy has been extensively studied in other cancers, including rectal and oesophageal cancers, among patients who achieved clinical CR after combined chemoradiotherapy. [However,] to our knowledge, this is the first in-depth analysis of CR in patients with HCC and the largest prospective series of patients with locally advanced HCC treated with neoadjuvant LRT-IO. It demonstrated that LRT-IO was associated with a durable response and that long-term survival was attainable in patients with CR,” concluded the researchers.
A previous study reported a CR rate of 42 percent among patients with locally advanced HCC treated with combined LRT plus IO (LRT-IO), however, data on predictors of CR and long-term survival without surgery and after discontinuation of IO were lacking. [Lancet Gastroenterol Hepatol 2023;8:169-178] “The objective of the present study was to assess the long-term clinical outcomes among patients with unresectable HCC who achieved CR after LRT-IO and were placed on a watch-and-wait protocol,” explained the researchers.
A total of 63 patients (median age, 69 years; male, 92.1 percent) with locally advanced, unresectable HCC (median tumour diameter, 10 cm; macrovascular invasion in 60.3 percent of patients) were treated with LRT (transarterial chemoembolization and/or stereotactic body radiotherapy) followed by at least one dose of IO (avelumab, nivolumab or pembrolizumab) at Queen Mary Hospital, Tuen Mun Hospital and University of Hong Kong–Shenzhen Hospital between January 2018 and December 2022. [JAMA Oncol 2024;doi:10.1001/jamaoncol.2024.4085]
At a median follow-up of 34.7 months, 46.0 percent of patients achieved CR, 28.6 percent achieved partial response, 9.5 percent had stable disease, and 15.9 percent experienced disease progression. Among patients with CR, 34.5 percent had Barcelona Clinic Liver Cancer stage A disease, while the rest had stage B or C disease. Patients who attained CR had significantly improved 3-year OS rates vs those who did not (75.5 vs 28.1 percent; 95 percent confidence interval [CI], 7.4–29.4; p<0.001). “Treatment response [hazard ratio, 5.10; 95 percent CI, 1.90–13.64; p=0.001] was the only independent factor associated with survival. Notably, there was no significant association between the duration of IO, type of LRT and grade ≥3 or higher immune-related adverse events [AEs] with CR,” reported the researchers.
The median time to CR was 5.4 months, while the median duration of CR was 25.7 months. Of patients with CR, 20.7 percent died before study completion due to HCC progression (6.9 percent), cardiac arrhythmia (6.9 percent), COVID-19 (3.4 percent), and cirrhosis (3.4 percent). At least one grade ≥3 treatment-related AE was experienced by 23.8 percent of patients, of which transient increases in alanine aminotransferase, aspartate aminotransferase or bilirubin levels (66.7 percent) were the most common. Immune-related AEs were reported in 12.7 percent of patients (hepatitis, 7.9 percent; dermatitis, 4.8 percent). Child-Pugh score deterioration of ≥2 was detected in 10.2 percent of patients at 3 months, 9.1 percent at 6 months and 6.2 percent at 12 months.
“The watch-and-wait strategy has been extensively studied in other cancers, including rectal and oesophageal cancers, among patients who achieved clinical CR after combined chemoradiotherapy. [However,] to our knowledge, this is the first in-depth analysis of CR in patients with HCC and the largest prospective series of patients with locally advanced HCC treated with neoadjuvant LRT-IO. It demonstrated that LRT-IO was associated with a durable response and that long-term survival was attainable in patients with CR,” concluded the researchers.