Frontline Atezolizumab and Bevacizumab Meet PFS, OS Endpoints in Phase III HCC Trial

Levi Garraway, MD, PhD

Levi Garraway, MD, PhD

Atezolizumab (Tecentriq) and bevacizumab (Avastin) demonstrated a statistically significant improvement in both progression-free survival (PFS) and overall survival (OS) compared with sorafenib (Nexavar) in patients with unresectable hepatocellular carcinoma (HCC) who have not received previous systemic therapy; this met both of the co-primary endpoints of the phase III IMbrave150 trial.¹

Findings from the IMbrave150 study will be submitted to regulatory authorities, including the FDA, European Medicines Agency, and the China National Medical Products Administration, according to a press release from Roche. Additional information about the PD-L1/VEGF inhibitor combination will also be presented at an upcoming medical meeting.

“We are very pleased with the results of our study testing the combination of Tecentriq and Avastin, which marks the first treatment in more than a decade to improve overall survival in people with unresectable hepatocellular carcinoma who have not received prior systemic therapy,” Levi Garraway, MD, PhD, chief medical officer and head of global product development, Roche, said in the press release. “HCC is a major cause of death globally and particularly in Asia, making this study an important step in our mission of addressing unmet medical needs for patients around the world. We will submit these data to global health authorities as soon as possible. Our hope is to bring a new treatment to people with this aggressive disease who currently have limited options.”

The open-label, randomized phase III trial is continuing to explore the combination of atezolizumab and bevacizumab in comparison with standard-of-care sorafenib in patients with previously untreated locally advanced or metastatic HCC (NCT03434379). Patients with an ECOG performance status of 0 or 1, Child-Pugh class A disease, and adequate hematologic and end-organ function are being randomized 2:1 to the experimental or control arm.

In the experimental arm, patients received 1200 mg atezolizumab intravenously plus 15 mg/kg bevacizumab intravenously, both given on day 1 of each 21-day cycle. Oral sorafenib was given in the control arm 400 mg twice daily in 21-day cycles.

Primary endpoints of OS and PFS improvement were determined by independent review per RECIST v1.1 criteria, and secondary endpoints included objective response rate (ORR), time to progression, duration of response, quality of life, safety, and pharmacokinetics.

Roche noted in their press release that the combination has not demonstrated any new safety signals and the toxicity profile is consistent with the known profile of the individual agents.

Bevacizumab was thought to enhance the ability of the PD-L1 inhibitor to restore antitumor immunity. Supporting the rationale of the combination, the FDA previously granted the combination a breakthrough therapy designation for the treatment of patients with HCC in July 2018, which was based off of the results of a phase Ib trial.

The trial was a multi-arm study that explored the use of the atezolizumab/bevacizumab combination in patients with gastrointestinal cancers. According to data presented at the 2018 ESMO Congress of 73 patients with previously untreated HCC who were evaluable for efficacy, the ORR was 32%, consisting of 1 complete response and partial responses in 22 patients.²

Median PFS by investigator assessment was 14.9 months, and the 6-month PFS rate was 65%. The median OS had not yet been reached as of the data cutoff. The median duration of response was ≥6 months in 52% of responders and ≥12 months in 26%.

By independent review, the ORR was 27%, and by HCC mRECIST criteria, the ORR was 34%.

Twenty-eight treatment-related grade 3/4 adverse events were observed in the study, 10 of which were hypertension.

References:

1. Roche’s Tecentriq in combination with Avastin increased overall survival and progression-free survival in people with unresectable hepatocellular carcinoma [media release]. Basel: Roche; October 21, 2019. https://bit.ly/2Mwd9Au. Accessed October 21, 2019.
2. Pishvaian MJ, Less MS, Ryoo B-Y, et al. Updated safety and clinical activity results from a Phase Ib study of atezolizumab + bevacizumab in hepatocellular carcinoma (HCC). Presented at: ESMO 2018; October 19-12, 2018; Munich, Germany. Abstract LBA26.