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Experts provide an overview of current systemic treatment options for 1st line uHCC, discussing the role of IO and IO-based combinations, along with emerging therapies and the latest clinical data. Topics also include: • Efficacy and safety of IO and IO combinations in HCC • How to select between the two 1st-line IO-based treatment options based on clinical factors • Future treatment in unresectable HCC Clinical Takeaways • Two 1st-line IO and IO-based combinations are approved for patients with unresectable hepatocellular carcinoma (HCC), with ongoing advancements shaping the treatment landscape • Clinical trials in newly diagnosed unresectable HCC patients have validated the effectiveness of IO plus anti-VEGF (atezolizumab + bevacizumab, IMbrave150) and dual IO (tremelimumab + durvalumab, HIMALAYA) approaches, establishing the proof of principle for these strategies • Landmark analysis is critical in IO-based treatments due to the delayed and continued separation of survival curves. Notably, the STRIDE regimen (single tremelimumab regular interval durvalumab) shows one in five patients achieving five-year survival in long-term follow-up • IO and IO-based regimens for unresectable HCC are generally well-tolerated, with immune-related adverse effects manageable using steroids when necessary • In clinical practice, treatment choice should be individualised, taking into account factors such as potential side effects and logistical considerations, including the frequency of hospital visits Website: http://www.oncbrothers.com/ X/Twitter: / oncbrothers Contact us at [email protected]