• Proteinuria is a common adverse event associated with Avastin.
• At trial enrolment, patients were tested for pre-existing proteinuria.
• Avastin management guidance was provided in the study protocol.
• The incidence of all grade proteinuria during the study was 30%.
• Patients could still continue single-agent therapy with Tecentriq if they discontinued Avastin due to proteinuria.

IMbrave150 was a Phase III, open-label, randomised study of Tecentriq in combination with Avastin compared with sorafenib, in patients with unresectable or advanced hepatocellular carcinoma (HCC) who had not received prior systemic therapy.[1]

Within 7 days prior to IMbrave150 trial initiation, patients underwent dipstick urinalysis for proteinuria. Table 1 shows the recruitment criteria.[2]

Table 1: Proteinuria analysis at IMbrave150 initiation

Table 2 shows the incidence of proteinuria in the IMbrave150 trial. In clinical trials investigating Tecentriq in combination with different therapies in different indications, all grade proteinuria arose at an of incidence of 8.2%.[3] In clinical trials studying Avastin in different indications, proteinuria arose within a range of 0.7% to 54.7% of patients receiving Avastin.[4] In these trials proteinuria ranged in severity from clinically asymptomatic, transient, trace proteinuria to nephrotic syndrome.[3,4]

Table 2. Incidence of all-cause proteinuria during IMbrave150 in safety-evaluable population [5]

Abbreviations: IV=intravenous; Q3W=every 3 weeks; bid=twice a day; Data Cutoff: Aug 31st 2020

Proteinuria was managed in the IMbrave150 trial as per Table 3.

Table 3. Management guidelines for proteinuria associated with Avastin [5]

The protocol of the IMbrave150 study allowed patients who discontinued either Tecentriq or Avastin due to adverse event to continue on single-agent therapy, until loss of clinical benefit or unacceptable toxicity associated with the single agent.[5] Table 4 shows the incidence of Avastin treatment interruptions and withdrawals due to proteinuria.

Table 4: Avastin treatment interruptions/dose modifications and withdrawals due to proteinuria [6]

Abbreviations: IV=intravenous; Q3W=every 3 weeks; bid=twice a day, Data Cutoff: Feb 2023

For further information related to Avastin-related proteinuria, please refer to the article "Monitoring and Management of Avastin-Associated Proteinuria".

1. Finn R, Qin S, Ikeda M, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med 2020;382:1894-1905. https://www.ncbi.nlm.nih.gov/pubmed/32402160
2. Protocol for: Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 2020;382:1894-905. DOI: 10.1056/NEJMoa1915745. Available at https://www.nejm.org/doi/suppl/10.1056/NEJMoa1915745/suppl_file/nejmoa1915745_protocol.pdf.
3. Roche Internal Regulatory Document, accessed on 03-Jul-2023.
4. Roche Internal Regulatory Document, accessed on 03-Jul-2023.
5. Cheng A, Qin S, Ikeda M, et al. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. See supplementary data " Multimedia component 4" for protocol and safety data. J Hepatol 2022;76:862-873. https://www.ncbi.nlm.nih.gov/pubmed/34902530
6. Roche Clinical Study Report, accessed on 14-Sept-2023.