receive systemic treatment.2 In advanced-


stage HCC patients (characterized by vascular invasion, lymphatic involvement or extrahepatic metastasis), tyrosine kinase inhibitors (TKIs) have been the mainstay of treatment since the 2008 SHARP trial over a decade ago. The SHARP (Sorafenib HCC Assessment Randomized Protocol) trial investigated 297 predominantly BCLC stage C HCC patients. It demonstrated that sorafenib produced a 31% reduction in risk of death and a 3-month increase in overall survival compared to placebo.3


Since


then, other single-agent TKIs (levantinib) and immunotherapies (nivolumab) have failed to show superiority.


TACE and immunotherapy for


intermediate-stage HCC “TIME” for combination trials? By Jacob Dayan, MD, and Joseph P. Erinjeri, MD, PhD


L cases.1


iver cancer is the third-leading cause of cancer death worldwide, of which hepatocellular carcinoma (HCC) represents 75–85% of Treatment algorithms for HCC


have remained fairly aligned to disease stage for the last 10 years. For example,


1984 1985


Self-expandable stents are created.


Barcelona clinic liver cancer (BCLC) stages 0 or A typically receive surgical or ablative therapy, stage B patients typically receive imaged-guided locoregional therapy like transarterial chemoembolization (TACE) or selective internal radiotherapy (SIRT), and stage C patients typically


1986 1987


Vertebroplasty is invented in France.


The rise of combination therapy However, in 2018, investigators in the IMbrave 150 trial proposed that a combination therapy (immunotherapy paired with an antiangiogenic) might improve the overall survival for advanced-stage HCC patients compared to sorafenib. Indeed, IMbrave 150 showed that combination of atezolizumab (anti PD-L1) and bevacizumab (antiangiogenic) had better overall survival than sorafenib alone, with a 67.2% vs 54.6% survival rate at 12 months.4


Perhaps more importantly,


the estimated percentage of patients with duration of response longer than 6 months was 87.6% in the atezo-bev group and 59.1% in the sorafenib group. The immunotherapy revolution, which has captivated patients’ hopes of longer survival through drugs that enhance their immune system, was finally underway in advanced-stage HCC. Other combination trials testing dual-agent immunotherapy (like the Himalaya trial) are currently underway in advanced-stage HCC.


1988 1989


The first carotid artery stenting takes place.


12 IRQ | SPRING 2021 SUPPLEMENT


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