A comprehensive real-world study across four Latin American countries has revealed that immune-related adverse events (irAEs) occur less frequently than expected in patients with unresectable hepatocellular carcinoma (HCC) receiving the standard combination therapy of atezolizumab and bevacizumab. The findings, published in Oncotarget, provide crucial insights for clinicians managing this aggressive form of liver cancer in everyday practice.
Lower Than Expected Toxicity Rates
The multicentric retrospective cohort study, encompassing 99 patients treated between 2019 and 2024 across Argentina, Brazil, Chile, and Colombia, found that only 18% of patients experienced immune-mediated toxicities. This represents a notably lower frequency compared to randomized clinical trials, where irAE rates typically exceed 30%.
"This study provides valuable insights into the incidence and impact of irAEs in patients with HCC treated with the combination of atezolizumab and bevacizumab in real-world practice," the researchers noted.
The predominant organ systems affected were the liver, manifesting as immune-mediated hepatitis, and the thyroid gland, causing thyroiditis. Most irAEs were classified as mild to moderate according to Common Terminology Criteria for Adverse Events (CTCAE) grades 1 or 2, with approximately half resolving within 30 days following appropriate clinical intervention.
Manageable Safety Profile
The study demonstrated that immune-related adverse events were generally manageable without aggressive immunomodulation. Only eight patients required steroid therapy for immune suppression, underscoring that most irAEs could be handled through standard clinical management protocols.
From a survival perspective, Kaplan-Meier analyses revealed no statistically significant difference in median overall survival between patients who developed irAEs and those who did not. Both groups exhibited identical median survival of 18.5 months, challenging previous hypotheses that immune toxicities correlate with enhanced antitumor efficacy.
Predictive Biomarker Identified
A particularly significant finding was the identification of elevated baseline alpha-fetoprotein (AFP) levels as a predictor for irAE development. Patients with AFP values exceeding 400 ng/mL showed significantly higher risk for experiencing immune-related adverse events.
"Notably, baseline alpha-fetoprotein (AFP) values ≥400 ng/ml were significantly associated with the development of irAEs," the researchers reported.
This predictive association could enable clinicians to implement intensified monitoring protocols or preemptive strategies in high-risk patients, potentially improving the safety profiles of immunotherapeutic regimens.
Real-World vs. Clinical Trial Differences
The study highlights important distinctions between real-world evidence and controlled clinical trial data. The lower irAE incidence observed may reflect differences in monitoring intensity, patient demographics, and healthcare infrastructure variations across Latin America compared to stringent trial environments.
Many enrolled patients had underlying cirrhosis or other chronic hepatic conditions that can complicate the immunological landscape, potentially masking or mimicking irAEs. This complexity necessitates nuanced clinical judgment to differentiate adverse events from disease progression or hepatic decompensation.
Clinical Implications for Latin American Populations
The research addresses a critical knowledge gap regarding immunotherapy responses in Latin American populations, who are often underrepresented in global clinical studies. The findings provide region-specific data that acknowledges local healthcare delivery variations and patient characteristics.
The study's lead authors, Leonardo Gomes da Fonseca from Hospital das Clínicas, Universidade de São Paulo, Brazil, and Federico Piñero from Hospital Universitario Austral, Argentina, emphasized the importance of multidisciplinary collaborations involving oncologists, hepatologists, and immunologists to optimize patient care.
Treatment Duration and Patient Characteristics
Patients received the atezolizumab and bevacizumab regimen for a median duration of approximately six months under routine clinical care. The cohort primarily consisted of patients with advanced unresectable HCC, many with underlying liver disease, reflecting the typical clinical presentation in Latin American healthcare settings.
The study reinforces that while irAEs require vigilant monitoring and individualized management, their occurrence does not inherently negate the therapeutic benefits of the atezolizumab-bevacizumab combination. Prompt recognition and tailored management strategies remain essential for optimizing patient outcomes while maintaining quality of life during treatment.
