FDA Approves Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma

June 1, 2020

The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

On May 29, 2020, the Food and Drug Administration approved atezolizumab in combination with bevacizumab (TECENTRIQ® and AVASTIN®, Genentech Inc.) for patients with unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy.

Efficacy was investigated in IMbrave150 (NCT03434379), a multicenter, international, open-label, randomized trial in patients with locally advanced unresectable or metastatic hepatocellular carcinoma who had not received prior systemic therapy. A total of 501 patients were randomized (2:1) to receive either atezolizumab 1200 mg as an intravenous infusion (IV) followed by bevacizumab 15 mg/kg IV on the same day, every 3 weeks, or sorafenib orally twice daily.

The main efficacy outcome measures were overall survival (OS) and independent review facility (IRF)-assessed progression-free survival (PFS) per RECIST 1.1. Additional efficacy outcome measures were IRF-assessed overall response rate (ORR) per RECIST 1.1 and mRECIST.

Median OS was not reached in the patients who received atezolizumab plus bevacizumab and was 13.2 months (95% CI: 10.4, NE) in the patients who received sorafenib (HR 0.58; 95% CI: 0.42, 0.79; p=0.0006). Estimated median PFS was 6.8 months (95% CI: 5.8, 8.3) vs. 4.3 months (95% CI: 4.0, 5.6), respectively (HR  0.59; 95% CI: 0.47, 0.76; p<0.0001). The ORR per RECIST 1.1 was 28% (95% CI: 23, 33) in the atezolizumab plus bevacizumab group compared with 12% (95% CI: 7,17) in the sorafenib group (p<0.0001). The ORR per mRECIST was 33% (95% CI: 28, 39) vs. 13% (95% CI: 8, 19), respectively (p<0.0001).

The most common adverse reactions (reported in ≥20% of patients) with atezolizumab plus bevacizumab in patients with HCC were hypertension, fatigue and proteinuria.

The recommended atezolizumab dose is 1,200 mg, followed by 15 mg/kg bevacizumab on the same day every 3 weeks. If bevacizumab is discontinued, atezolizumab should be given either as 840 mg every 2 weeks, 1,200 mg every 3 weeks, or 1,680 mg every 4 weeks.

View full prescribing information for TECENTRIQ.

View full prescribing information for AVASTIN.

FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, and Singapore’s Health Sciences Authority (HSA) on the review of the atezolizumab application as part of Project Orbis. FDA approved this application nearly two months ahead of schedule. The review of the atezolizumab application is ongoing for the Australian TGA, Health Canada and Singapore’s HSA.

This review used the Real-Time Oncology Review (RTOR), which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

These applications were granted priority review and atezolizumab and bevacizumab received breakthrough designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

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