Time toxicity in patients treated with atezolizumab plus bevacizumab or sorafenib within the IMbrave 150 trial

Hepatocellular carcinoma (HCC), the most common primary liver cancer, is the fourth cause of cancer-related death worldwide. Sorafenib (oral drug that inhibits cancer growth by blocking blood vessels formation), has been the only available treatment for advanced HCC for more than a decade. In 2020, the combination of atezolizumab (immune checkpoint inhibitor [ICI], a type of treatment that helps the immune system seek out and destroy cancer) and bevacizumab (targeted therapy that starves tumors by preventing new blood vessels from growing) has demonstrated significant survival advantage over sorafenib in treatment-naïve (patients who have never received treatment) advanced HCC. Moreover, the combination has proved superior even in terms of patient-reported outcomes (PROs), allowing patients to maintain good quality of life (QoL), physical function (possibility to carry out daily) and role function (ability to fulfil specific responsibilities in social settings).

Although, in recent years there has been an increasing awareness within the oncology field of the need to acknowledge and quantify the impact of the time patients spend pursuing cancer treatment -referred to as time toxicity- on both survival and QoL. Time toxicity encompasses the number of days patients spend receiving cancer treatment, attending follow-up or urgent care visits, or hospitalized. When a limited survival is expected, frequent interactions with the healthcare system may erode meaningful survival time (time that could be spent at home, engaging in everyday activities, or with loved ones) thereby potentially offsetting the benefits of active-anticancer therapy.

Necessity of the research: Time toxicity has been evaluated in many cancer types; however, no evidence is available regarding its impact in patients with advanced HCC candidate to systemic therapy. Furthermore, only one study has explored the role of time toxicity in deterioration of QoL and functional status in cancer patients. In that study, higher time toxicity was correlated with a decline in physical functioning (reduced ability to perform activities of daily living, such as eating, dressing, washing, or being physically active) but not with a deterioration of global health status which reflects patients’ overall perception of their health and QoL.

In this proposal, we aim to evaluate time toxicity and its impact on patients reported outcomes in patients treated within the IMbrave 150 study, comparing the expected burden secondary to each cancer treatment in patients treated with atezolizumab plus bevacizumab and in a control cohort treated with sorafenib. We will also try to identify baseline characteristics associated with a higher time toxicity in these patients.

How the research will add to medical science or patient care: Access to the IMbrave150 dataset is likely to be highly contributory to this topic, providing high quality data to paint a clearer picture of time toxicity, its impact and the baseline features associated to it in HCC patients.