Underlying liver disease does not affect HCC survival after immune checkpoint inhibition
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The benefit of immune checkpoint inhibitor therapy for hepatocellular carcinoma did not vary by underlying liver disease, according to study results presented at ASCO Gastrointestinal Cancers Symposium.
Patients with viral-induced HCC achieved numerically longer OS than those with nonviral-induced disease; however, the difference did not reach statistical significance.
“Further studies with increased granularity are needed to more clearly identify patients with unresectable HCC who are more likely to have better outcomes with immunotherapy,” researcher Linda Wu, MD, fellow in hematology and medical oncology at Mount Sinai Hospital, told Healio.
Immune checkpoint inhibitors — either alone or in combination with bevacizumab (Avastin, Genentech) — have become a standard treatment for patients with unresectable HCC. Although this class of agents has improved HCC outcomes, only a small percentage of patients respond.
“[This highlights] the need to identify biomarkers to improve patient selection,” Wu said. “Emerging evidence suggests that patients with nonviral causes of HCC, particularly nonalcoholic steatohepatitis (NASH), may not derive the same benefit with immunotherapy as those with viral causes. We hoped to use real-world data to evaluate whether patients with viral HCC have improved survival outcomes when treated with immunotherapy compared with patients with nonviral HCC.”
Wu and colleagues performed a retrospective chart review of 349 patients (median age, 63 years; 84% male) with unresectable HCC treated with immune checkpoint inhibitors between January 2017 to June 2021 at Mount Sinai Health System. Researchers characterized the majority (86%) of patients as cirrhotic.
Most patients (70%) had HCC with viral etiology, with two-thirds (67.5%) of these cases due to hepatitis C infection. Thirty percent of patients had nonviral causes of HCC, with the most common causes being NASH (47%) and alcohol (39%).
The majority of patients had Child-Pugh class A liver disease (66%) and ECOG performance status of 0 (71%) at the time of immune checkpoint inhibitor initiation.
Most patients (79%) received immune checkpoint inhibitors as first-line therapy, and the majority (87%) received nivolumab (Opdivo, Bristol Myers Squibb).
The difference in OS between patients with viral etiologies and nonviral etiologies of HCC served as the primary outcome. These groups appeared balanced with regard to age, sex, cirrhosis, ECOG performance status, line of therapy and type of immune checkpoint inhibitor received.
After median follow-up of 10.5 months (range, 1.4-62.4), researchers reported longer median OS among patients with viral HCC (19.3 months; 95% CI, 14.2-26.6) than nonviral HCC (11.4 months; 95% CI, 9.3-17.7). However, the difference — after adjustment for Child-Pugh class and disease stage — did not reach statistical significance (HR = 0.81; 95% CI, 0.58-1.12).
“The lack of statistical significance was somewhat surprising, as multiple studies have now shown this trend toward improved survival among patients with viral HCC treated with immunotherapy,” Wu told Healio. “However, the study may have been underpowered.”
The result underscores the need to better define subgroups of patients most likely to benefit from immunotherapy, Wu added.
“Although immunotherapy has revolutionized treatment of advanced unresectable HCC, only approximately one-third of patients respond, based on the IMbrave150 trial,” Wu said. “Additional research into biomarker discovery for response to immunotherapy is important to optimize patient selection, and we hope that matching patients with optimal therapy would also improve patient outcomes.”
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Wu YL, et al. Abstract 396. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 20-22, 2022; San Francisco.
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