Atezolizumab/Bevacizumab Is Favored for Further Study in HCC

Joseph Kim, MD

Because the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) has demonstrated superiority over sorafenib (Nexavar), it has become the new standard in the frontline treatment of patients with unresectable hepatocellular carcinoma (HCC), according to Joseph Kim, MD. Due to this success, the regimen is now under examination in the adjuvant setting.

“In patients with advanced or metastatic HCC, [atezolizumab/bevacizumab] has become the gold standard. This is really the first-line option for patients with advanced HCC, and it has really come to the forefront of treatment,” said Kim. “The results of this trial have been so promising and positive that the IMbrave050 trial has been organized and is now open.”

In May 2020, the FDA approved atezolizumab plus bevacizumab for use in patients with unresectable or metastatic HCC who have not received any prior systemic therapies, according to data from the IMbrave150 study (NCT03434379).¹ Updated results, which were presented during the 2021 Gastrointestinal Cancers Symposium, showed a median overall survival of 19.2 months with the combination versus 13.4 months with sorafenib (HR, 0.66; 95% CI, 0.52-0.85; P = .0009). The median progressionfree survival was 6.9 months versus 4.3 months, respectively (HR, 0.65; 95% CI, 0.53-0.81; P = .0001).²

Investigators have also launched the phase 3 IMbrave050 trial (NCT04102098) to examine the safety and efficacy of atezolizumab/bevacizumab as an adjuvant treatment versus active surveillance in patients with completely resected or ablated HCC who are at increased risk for recurrence.³

In an interview with OncLive® during a 2020 Institutional Perspectives in Cancer webinar on gastrointestinal malignancies, Kim, a surgical oncologist with the University of Kentucky Markey Cancer Center, discussed the multidisciplinary management of patients with HCC.

OncLive®: Why is HCC a complicated disease to treat?

Kim: Some medical issues associated with this disease, including cirrhosis and other risk factors, come into play. Also, important surgical issues need to be considered. When surgical options are not available, we need to think of other locoregional therapeutic options like radiation therapy, chemoembolization, and radioembolization. Finally, systemic therapies are becoming increasingly important for patients with HCC. [Optimal management] of patients with this disease really requires multidisciplinary input from all our specialists.

Many [professionals in the] oncology community feel that the new gold standard for managing patients with advanced HCC is the combination of atezolizumab, an immune checkpoint inhibitor, along with bevacizumab, a monoclonal antibody targeting the major angiogenesis factor VEGF.

Could you expand on what these multidisciplinary efforts look like?

When patients with cancer present to our center, and I expect this is true across all US cancer centers, their cases are presented at multidisciplinary tumor boards. This is done so that all the experts involved in the care of patients with this cancer can provide their expertise so that the best possible treatment [approach] can be formulated.

First, [we have] the radiologist, who is the expert in interpreting the imaging studies, and the pathologist, who reviews the biopsy if one has been performed. We have our radiation oncologists, our medical oncologists, and our surgeons, who may include our transplant surgeons and hepatobiliary surgeons. All these different disciplines are involved in the optimal management of this population.

How do you approach treatment selection? What does your treatment algorithm look like?

I worked with one of my previous surgical oncology fellows to put together a simple algorithm to follow. The first category of treatments includes the curative options. The best-case scenario for patients with HCC would be if they had disease that could undergo curative surgical treatment, including surgical resection of disease. However, that’s often limited because of the patient’s degree of cirrhosis or liver injury. The second option would be liver transplant, which would potentially treat the cirrhosis, as well as cure the cancer, and ablation of the disease, which can be performed either by the surgeon in the operating room or by the interventional radiologist in the radiology department.

If surgery is not possible and the disease is advanced but still remains in the liver, patients would be eligible for these regional or liver-directed therapies. Again, these would include chemoembolization, radioembolization, and external beam radiation treatment to the tumor. These treatments have been shown to be beneficial for patients with HCC.

If patients have disease that has spread outside of the confines of the liver—metastatic disease—or they have locally advanced disease that is not amenable to these surgeries or regional therapies, they are eligible for the systemic or targeted therapies. The first biologic or targeted therapy that was shown to be beneficial in this disease was sorafenib back in 2008. More recently, immune checkpoint inhibitors and other targeted drugs have been found to provide overall survival [OS] benefit for patients with HCC.

Going back to atezolizumab and bevacizumab, what is most significant about the IMbrave150 trial?

The trial demonstrated that the combination was superior to the previous gold standard, which was sorafenib, which had been proven to be beneficial in patients with HCC back in 2008. However, in many circumstances and in my own experience, this drug is quite toxic and has not provided the type of survival benefit or the type of disease control that we have sought for patients with this disease.

This new drug combination, atezolizumab plus bevacizumab, is not only superior to sorafenib but is also safer and better tolerated. It wins on both fronts: Patients are able to tolerate and endure the combination and [they are achieving an] OS benefit.

How will the phase 3 IMbrave050 trial provide additional insight on this regimen?

[Because data from the IMbrave150] trial have been so promising, IMbrave050 has been [launched] and is now open here, at the University of Kentucky, and elsewhere across the United States to see whether patients who are eligible and who undergo surgical resection of their HCC would benefit by receiving this drug combination as an adjuvant therapy following surgery. We’re looking for ways to see whether this combination can be used in other settings for patients with HCC; that’s how promising this regimen has been.

Where should future efforts be focused?

HCC is a disease that has been difficult to treat in the past. We still have improvements to make in the early detection of the disease, and we need to better refine how we’re going to use the drugs that have been shown to be effective. Many of the drugs that are active nowadays have been shown to work in the second-line setting after another approach has failed. We have to reexamine the paradigm that has been put in place in terms of which drugs we use first, which ones we use second, and now which drugs we use third. We might see a reshuffling of how these drugs are being used. That is going to be a future focus [of research] in the management of patients with HCC.

References

1. FDA approves Genentech’s Tecentriq in combination with Avastin for people with the most common form of liver cancer. News release. Genentech. May 29, 2020. Accessed December 14, 2020. https://bit.ly/2Aneztc.
2. A study of atezolizumab plus bevacizumab versus active surveillance as adjuvant therapy in patients with hepatocellular carcinoma at high risk of recurrence after surgical resection or ablation (IMbrave050). ClinicalTrials.gov. Updated December 23, 2020. Accessed December 14, 2020. https://www.clinicaltrials.gov/ct2/show/NCT04102098.