Beta blocker use does not affect outcomes in immunotherapy-treated HCC
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Use of beta blockers did not affect outcomes among patients treated with immunotherapy for unresectable hepatocellular carcinoma, according to study results presented at ASCO Gastrointestinal Cancers Symposium.
Researchers reported comparable OS and overall response rates between those who used beta blockers and those who did not.
“More studies are required to better elucidate the effect of beta blockade and portal hypertension on HCC and immunotherapy,” researcher Linda Wu, MD, fellow in hematology and medical oncology at Mount Sinai Hospital, told Healio.
Despite treatment advances, prognosis for patients with advanced unresectable HCC remains poor.
“There is increasing evidence that the tumor microbiome may play a role in response to immunotherapy,” Wu said. “In fact, there is evidence that portal hypertension plays a role in dysbiosis and promotes progression of liver disease, and beta blocker use may reduce risk of HCC and improve OS [for] patients with HCC. We hoped to evaluate using real-world data whether beta blocker use can improve the survival of patients with unresectable HCC treated with immunotherapy.”
Researchers conducted a retrospective chart review of 578 patients (median age, 65 years; 80% male) with unresectable HCC treated with immune checkpoint inhibitors between 2017 and 2019 at 13 institutions in North America, Asia and Europe.
Investigators classified 70% of patients as cirrhotic. Causes of underlying liver disease included hepatitis C virus (36%), hepatitis B virus (22%), alcohol (20.8%) and nonalcoholic steatohepatitis (13%).
Nearly three-quarters (73.5%) of patients had Child-Pugh class A liver disease, and nearly all had ECOG performance status of 0 (52%) or 1 (45%).
Most patients (75%) received a PD-1 inhibitor alone.
Approximately one-third (35%; n = 203) had used beta blockers at any point during immune checkpoint inhibitor therapy. A comparable percentage used nonselective (51%) and cardio-selective (49%) beta blockers.
Wu and colleagues used univariable and multivariable logistic regression models to assess associations between beta blocker use and OS or ORR.
After median follow-up of 30.8 months (interquartile range, 17.2-40.3), 360 patients (62%) died.
Univariate and multivariate analyses revealed no statistically significant correlation between beta blocker use and OS (HR = 1.12; 95% CI, 0.9-1.39) or ORR (OR = 0.84; 95% CI, 0.54-1.31).
“Although many patients with HCC and cirrhosis are on beta blockers at baseline, beta blocker use did not affect outcomes of patients with HCC treated with immunotherapy,” Wu told Healio. “In addition, the type of beta blockers used — such as cardioselective vs. nonselective — did not play a role. We had hoped that modulation of portal hypertension would improve response to therapy.”
Further studies are necessary to assess the effect of cirrhosis and portal hypertension on the response to immunotherapy among patients with unresectable HCC, as well as their interaction with the tumor microbiome and immune activation, Wu said.
“We also hope to conduct further studies to evaluate the effect of antibiotics and beta blocker use on outcomes of immunotherapy in HCC,” Wu said.
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Wu L, et al. Abstract 399. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 20-22, 2022; San Francisco.
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