This is an observational study in which only data will be collected from adults with unresectable hepatocellular carcinoma. These adults should be prescribed a different treatment after treatment with atezolizumab and bevacizumab, or another similar combination of drugs, by their doctors.

Unresectable hepatocellular carcinoma (uHCC) is a type of liver cancer that cannot be treated with surgery.

In the past, sorafenib was the only approved first-line anti-cancer drug for people with uHCC. Regorafenib and other drugs were approved as second-line treatments for uHCC if a person could not take sorafenib or it stopped working for them.

Lately, another first-line (1L) treatment called immuno-oncology (IO) immune checkpoint inhibitor combination (1L-IO combo), like atezolizumab with bevacizumab (AB), has become the preferred choice of treatment. This is because of the meaningful impact on patient survival. 1L-IO combo are drugs that help the body's defense system recognize and kill cancer cells.

Since the other treatments were previously approved for use following sorafenib, the best order to take these treatments in following an 1L-IO combo is unknown.

To better understand and determine this order, more knowledge is needed about how well different treatments work in participants with uHCC who have been treated with AB or another 1L-IO combo.

The main purpose of this study is to learn more about how well different treatments work when given after first-line treatment with AB or another approved 1L-IO combo. To do this, researchers will collect data on how long the participants live (also called overall survival) from the start of any treatment given after the first-line treatment.

In addition, researchers will also collect the following information to learn more about the participants who will be given a different treatment after the 1L-IO combo:

• characteristics including age, sex, and race, and signs and symptoms of the participants over the duration of their first-line treatment
• the length of time from the first to the last dose (also called duration of therapy) of the treatments given after the 1L-IO combo
• the length of time until a participant's cancer worsens, or they die (also called progression free survival) from the start of the treatments given after the 1L-IO combo
• the number of participants whose tumor completely disappears or shrinks (also called overall tumor response) after taking the treatments given after the 1L-IO combo
• the sequence of treatments given after the 1L-IO combo Data will be collected from September 2023 to December 2026 and cover a period of around 3 years. The data will be collected using medical records or by interviewing the participants during their routine visits to the doctor.

Researchers will observe participants from the start of the treatment given after the 1L-IO combo until the end of their participation in the study.

In this study, only data from routine care will be collected. No visits or tests are required as part of this study.

Inclusion Criteria:

• Adult patients, ≥ 18 years of age on the day of signing informed consent.
• Confirmed diagnosis of uHCC, treated in a first-line setting with AB or another approved 1L-IO combo therapy.
• Decision to initiate treatment with a second-line systemic treatment was made as per investigator's routine treatment practice prior to study enrollment.
• Signed informed consent or (for patients under legal age) signed informed assent by the patient (where applicable) and signed informed consent by parents / legal guardian.
• No participation in an investigational program with interventions outside of routine clinical practice.

Exclusion Criteria:

- Not applicable

Patients with a diagnosis of uHCC treated with first-line AB or another approved 1L-IO combo and in whom a decision to treat with a second-line of systemic therapy has been made by the treating physician. The investigator or a delegate at these centers collects historic data (demographic and clinical characteristics) from medical records if available. The investigator or a delegate collects treatment-related data during visits that take place in routine practice.

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.