Roche's Tecentriq Plus Avastin Approved in Europe for First-Line Treatment of Unresectable Hepatocellular Carcinoma

Compiled by Keke

On November 2, Roche announced that the European Commission has approved Tecentriq® (atezolizumab) in combination with Avastin® (bevacizumab) for the treatment of adult patients with unresectable or advanced hepatocellular carcinoma (HCC) who have not received prior systemic therapy.

This approval was based on the results of the Phase 3 clinical study IMbrave150, a global, multicenter, open-label study that enrolled 501 patients with unresectable hepatocellular carcinoma (HCC) who had not previously received systemic therapy. Participants were randomized in a 2:1 ratio to receive either Tecentriq in combination with bevacizumab or sorafenib. Patients in the combination arm received intravenous Tecentriq 1200 mg and bevacizumab 15 mg/kg on Day 1 of each 21-day cycle; sorafenib was administered orally at 400 mg twice daily on Days 1–21 of each 21-day cycle. Patients received either the combination therapy or sorafenib until disease progression or unacceptable toxicity occurred. The two primary endpoints were overall survival (OS) and progression-free survival (PFS) as assessed by an independent review facility (IRF) according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Other study endpoints included the objective response rate (ORR) as assessed by the IRF according to RECIST v1.1 and the modified RECIST for HCC (mRECIST).

This study demonstrated that, compared with sorafenib, Tecentriq in combination with bevacizumab reduced the risk of death (overall survival [OS]) by 42% (hazard ratio [HR]=0.58; 95% CI: 0.42–0.79; p=0.0006) and reduced the risk of disease progression or death (progression-free survival [PFS]) by 41% (HR=0.59; 95% CI: 0.47–0.76; p<0.0001). IMbrave150 is the first Phase III clinical trial of cancer immunotherapy to show improvements in both OS and PFS (compared with sorafenib) in patients with unresectable hepatocellular carcinoma. In terms of safety, grade 3–4 adverse events occurred in 57% of patients receiving Tecentriq plus bevacizumab, compared with 55% of those receiving sorafenib. The most common serious adverse reactions (≥2%) associated with the combination therapy were gastrointestinal hemorrhage and pyrexia.

This approval follows the positive recommendation issued by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in September 2020. In May 2020, the U.S. Food and Drug Administration (FDA) approved Tecentriq in combination with Avastin for the treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC) who had not previously received systemic therapy. Additionally, China’s National Medical Products Administration approved this combination therapy in October 2020 for the treatment of patients with unresectable HCC who had not previously undergone systemic therapy. Furthermore, Tecentriq combined with Avastin has recently been listed as a Category I recommended regimen by the European Society for Medical Oncology (ESMO) for the treatment of unresectable HCC.

Tecentriq is a monoclonal antibody designed to bind to the PD-L1 protein, which is expressed on tumor cells and tumor-infiltrating immune cells, thereby blocking its interaction with the PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq can activate T cells. As a cancer immunotherapy, this drug may serve as a foundational combination partner with other immunotherapies, targeted agents, and various chemotherapy regimens across a broad range of cancers. Tecentriq has previously been approved for use as monotherapy or in combination with various forms of targeted therapy and/or chemotherapy for the treatment of non-small cell lung cancer, small cell lung cancer, certain types of metastatic urothelial carcinoma, and PD-L1-positive metastatic triple-negative breast cancer. In the United States, Tecentriq is also approved in combination with Cotellic® (cobimetinib) and Zelboraf® (vemurafenib) for the treatment of patients with BRAF V600 mutation-positive advanced melanoma.

Avastin is an intravenously administered monoclonal antibody that specifically binds to a protein called vascular endothelial growth factor (VEGF). VEGF plays a critical role throughout the tumor lifecycle, primarily in the development and maintenance of blood vessels, a process known as angiogenesis. Tumor blood supply is considered key to tumor growth and spread (metastasis) within the body. Avastin exerts its anti-angiogenic effect by directly binding to VEGF, thereby preventing its interaction with receptors on vascular endothelial cells and disrupting the tumor’s blood supply. Furthermore, by inhibiting VEGF-mediated immunosuppression, promoting T-cell infiltration into tumors, and initiating T-cell responses against tumor antigens, Avastin can further enhance Tecentriq’s ability to restore anti-cancer immunity. Therefore, the combination therapy of Tecentriq and Avastin can amplify the potential of the immune system to combat various cancers.

Reference Source:

• Tecentriq in combination with Avastin is the first and only cancer immunotherapy regimen approved in Europe for the treatment of unresectable hepatocellular carcinoma (HCC), the most common form of liver cancer

• Tecentriq combination improved overall