Atezolizumab Combo Improves Survival in Unresectable HCC

A new combination may help with overall and progression-free survival in liver cancer.

Atezolizumab (Tecentriq) administered in combination with bevacizumab (Avastin) improved overall (OS) and progression-free survival (PFS), compared with standard-of-care sorafenib (Nexavar) in patients with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapies, according to Roche.

Data from the phase III IMbrave150 trial – which met both of its co-primary endpoints of demonstrating statistically significant and clinically meaningful improvements in OS and PFS – is not yet available; however, it will be presented at an upcoming medical meeting.

“We will submit these data to global health authorities as soon as possible,” added Levi Garraway, MD, PhD, chief medical officer and head of global product development for Roche, in a statement issued by the company.

The phase III IMbrave150 trial is an open-label, multicenter study of 501 participants with unresectable HCC who have been randomized 2:1 to receive either atezolizumab plus bevacizumab or the current standard of care. The experimental group received 1200 mg atezolizumab IV and 15 mg/kg bevacizumab IV, both on day 1 of each 21-day cycle. The standard-of-care arm received 400 mg oral sorafenib twice daily, each day of the 21-day cycle.

Co-primary endpoints were OS and PFS by independent-review facility (IRF) per RECIST v1.1. Secondary endpoints included overall response rate, time to progression and duration of response, as measured by RECIST v1.1 (investigator-assessed [INV] and IRF) and HCC mRECIST (IRF), as well as patient-reported outcomes, safety, and pharmacokinetics.

In addition, researchers found no new safety signals associated with the combination regimen.

The FDA granted the combination breakthrough therapy designation for in July 2018, based on data from an ongoing phase Ib trial.

Garraway noted the combination would mark “the first treatment in more than a decade to improve overall survival” for patients with unresectable HCC.

“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,” he added.

Kristen Spencer, DO, MPH, a medical oncologist from the Rutgers Cancer Institute of New Jersey not involved in the work, told CancerNetwork® by email that trends suggest HCC incidence is on the rise-and overall treatment options have been limited.

“As a field we have for some time been seeking to capture the robust responses that have been offered by immunotherapeutic approaches in some advanced malignancies,” she said. “To date the response rate to checkpoint monotherapy has been modest, but the durable responses seen have been promising. Combination strategies including an immunotherapy backbone have been eagerly pursued."

The new trial could offer some new insights, depending on how the results bear out, added Spencer.

“We will certainly need to review specific data from IMbrave150 to determine if these statistically significant results are clinically meaningful, but data from earlier studies have been promising, and we eagerly anticipate the presentation of the data.”

The company said it was working on “extensive development program” for atezolizumab including multiple ongoing and planned phase III trials in lung, genitourinary, skin, breast, gasotrintestinal, gynecological, and head and neck cancers.

Since atezolizumab is a monoclonal antibody aimed at inhibiting PD-L1, its combination with the VEGF-protein-targeting bevacizumab to cut off tumor blood supply is seen as a one-two punch which could make a significant difference in some tumors, the company said in a statement issued to CancerNetwork.

“The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers,” it said. 



Hoffman-La Roche. A Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma [IMbrave150] (IMbrave150). Available from: NLM identifier: NCT03434379. Accessed October 21, 2019.