“Absolutely, 100%, this is a practice-changing paper, because no other trial has beaten sorafenib so far and shown superiority. The trial shows a difference in OS, greater response rate, and longer PFS. This will be a first-line treatment for a lot of patients, and I don’t think sorafenib or lenvatinib will be used anymore; I’d use this [new] combination over both now,” said Dr Wong.

“Sorafenib is a tough drug — when it works, it’s great — but often, it doesn’t work and people muddle through the side effects or toxicities while we try to find out if there is any benefit,” said Mary F. Mulcahy, MD, professor of medicine, radiology, and surgery at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago, Illinois. “Anything better tolerated with better quality of life with a survival benefit; this will be a good first-line option,” added Dr Mulcahy.

The rate of grade 3 or 4 adverse events was slightly higher in the combination treatment group than in the sorafenib group (56.5% vs 55.1%, respectively).

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“When we looked at the adverse events — it doesn’t stand out that there’s any 1 event that dominates the increased side-effect profile. Bevacizumab has always had bleeding concerns; liver cancer always has bleeding concerns. It comes down to patient selection that will include patients who don’t have significant varices coming on to the study,” said Dr Finn.

But if sorafenib alone is already well known to be a poorly tolerated treatment, will a combination regimen with what appears to be a similar incidence of adverse events hold adoption of that regimen back?

“The bevacizumab-related adverse events, hypertension, and proteinuria are manageable for the most part, but the adverse events like bleeding — that’s a concern. This is a very select patient group involved in this study because of this risk for bleeding, and we are going to need to maintain this selection criteria for putting people on this regimen,” said Dr Mulcahy.

However, despite the similar levels of grade 3 and grade 4 adverse events, the patient-reported QoL outcomes were different, with the patients on the combination treatment reporting greater QoL scores than the scores reported by patients receiving sorafenib.

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“The quality-of-life measure was striking, which is very important for these studies. Liver cancer is one we aren’t curing; the goal of these therapies isn’t curative. Not only is the survival benefit there, people have a better quality of life,” said Dr Mulcahy.

The trial results and subsequent approval of the combination therapy represent a first major step in the treatment of advanced HCC since sorafenib was approved for the indication in 2007 — and physicians involved in the field are hoping that more combination therapy strategies will follow.

“There’s a lot coming down the pipeline — looking at different immunotherapies such as nivolumab and ipilimumab with different tyrosine kinase inhibitors such as sorafenib, lenvatinib, cabozantinib … we have to understand how to use these in combinations or sequentially to give patients [the] best benefit,” said Dr Mulcahy.

Disclosure: The NEJM trial discussed in this article was funded by F. Hoffmann–La Roche/Genentech. For a full list of author disclosures, please refer to the original study.


  1. Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894-1905.
  2. Finn RS, Qin S, Ikeda M, et al. Time to response and characteristics of patients who had complete responses in IMbrave150: A phase III clinical trial of atezolizumab + bevacizumab for unresectable hepatocellular carcinoma (HCC). Poster presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 4596.
  3. Genentech. FDA approves Genentech’s Tecentriq in combination with Avastin for people with the most common form of liver cancer [press release]. Published May 29, 2020. Accessed June 10, 2020.